CD133 expression in chemo-resistant Ewing sarcoma cells View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2010-03-26

AUTHORS

Xiaohua Jiang, Ynnez Gwye, Darren Russell, Christine Cao, Dorothea Douglas, Long Hung, Heinrich Kovar, Timothy J Triche, Elizabeth R Lawlor

ABSTRACT

BackgroundSome human cancers demonstrate cellular hierarchies in which tumor-initiating cancer stem cells generate progeny cells with reduced tumorigenic potential. This cancer stem cell population is proposed to be a source of therapy-resistant and recurrent disease. Ewing sarcoma family tumors (ESFT) are highly aggressive cancers in which drug-resistant, relapsed disease remains a significant clinical problem. Recently, the cell surface protein CD133 was identified as a putative marker of tumor-initiating cells in ESFT. We evaluated ESFT tumors and cell lines to determine if high levels of CD133 are associated with drug resistance.MethodsExpression of the CD133-encoding PROM1 gene was determined by RT-PCR in ESFT tumors and cell lines. CD133 protein expression was assessed by western blot, FACS and/or immunostaining. Cell lines were FACS-sorted into CD133+ and CD133- fractions and proliferation, colony formation in soft agar, and in vivo tumorigenicity compared. Chemosensitivity was measured using MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxy-methoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assays.ResultsPROM1 expression was either absent or extremely low in most tumors. However, PROM1 was highly over-expressed in 4 of 48 cases. Two of the 4 patients with PROM1 over-expressing tumors rapidly succumbed to primary drug-resistant disease and two are long-term, event-free survivors. The expression of PROM1 in ESFT cell lines was similarly heterogeneous. The frequency of CD133+ cells ranged from 2-99% and, with one exception, no differences in the chemoresistance or tumorigenicity of CD133+ and CD133- cell fractions were detected. Importantly, however, the STA-ET-8.2 cell line was found to retain a cellular hierarchy in which relatively chemo-resistant, tumorigenic CD133+ cells gave rise to relatively chemo-sensitive, less tumorigenic, CD133- progeny.ConclusionsUp to 10% of ESFT express high levels of PROM1. In some tumors and cell lines the CD133+ fraction is relatively more drug-resistant, while in others there is no apparent difference between CD133+ and CD133- cells. These studies reveal heterogeneity in PROM1/CD133 expression in ESFT tumors and cell lines and confirm that high levels of PROM1 expression are, in at least some cases, associated with chemo-resistant disease. Further studies are required to elucidate the contribution of PROM1/CD133 expressing cells to therapeutic resistance in a large, prospective cohort of primary ESFT. More... »

PAGES

116

References to SciGraph publications

  • 2008-06-06. The utility and limitations of glycosylated human CD133 epitopes in defining cancer stem cells in JOURNAL OF MOLECULAR MEDICINE
  • 2006-12-02. Analysis of gene expression and chemoresistance of CD133+ cancer stem cells in glioblastoma in MOLECULAR CANCER
  • 2002-01-10. Anchorage-independent multi-cellular spheroids as an in vitro model of growth signaling in Ewing tumors in ONCOGENE
  • 1997-10-30. Among genes involved in the RB dependent cell cycle regulatory cascade, the p16 tumor suppressor gene is frequently lost in the Ewing family of tumors in ONCOGENE
  • 2006-11-19. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice in NATURE
  • 2004-11. Identification of human brain tumour initiating cells in NATURE
  • 2006-07-16. Transformation from committed progenitor to leukaemia stem cell initiated by MLL–AF9 in NATURE
  • 2005-06-29. Summing up cancer stem cells in NATURE
  • 2006-10-18. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response in NATURE
  • 2007-07-26. ATP-binding-cassette transporters in hematopoietic stem cells and their utility as therapeutical targets in acute and chronic myeloid leukemia in LEUKEMIA
  • 2007-09-24. CD133+ HCC cancer stem cells confer chemoresistance by preferential expression of the Akt/PKB survival pathway in ONCOGENE
  • 2008-12-01. Efficient tumour formation by single human melanoma cells in NATURE
  • 1997-07. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell in NATURE MEDICINE
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/1471-2407-10-116

    DOI

    http://dx.doi.org/10.1186/1471-2407-10-116

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1032569982

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/20346143


    Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
    Incoming Citations Browse incoming citations for this publication using opencitations.net

    JSON-LD is the canonical representation for SciGraph data.

    TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

    [
      {
        "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
        "about": [
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Medical and Health Sciences", 
            "type": "DefinedTerm"
          }, 
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1112", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Oncology and Carcinogenesis", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "AC133 Antigen", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Animals", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Antigens, CD", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cell Separation", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cohort Studies", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Drug Resistance, Neoplasm", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Flow Cytometry", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Gene Expression Regulation, Neoplastic", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Glycoproteins", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Humans", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Mice", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Mice, Inbred NOD", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Mice, SCID", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Peptides", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Recurrence", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Reverse Transcriptase Polymerase Chain Reaction", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Sarcoma, Ewing", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "Saban Research Institute, Childrens Hospital Los Angeles, 4650 Sunset Blvd, 90027, Los Angeles, CA, USA", 
              "id": "http://www.grid.ac/institutes/grid.239546.f", 
              "name": [
                "Saban Research Institute, Childrens Hospital Los Angeles, 4650 Sunset Blvd, 90027, Los Angeles, CA, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Jiang", 
            "givenName": "Xiaohua", 
            "id": "sg:person.01207627037.15", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01207627037.15"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Saban Research Institute, Childrens Hospital Los Angeles, 4650 Sunset Blvd, 90027, Los Angeles, CA, USA", 
              "id": "http://www.grid.ac/institutes/grid.239546.f", 
              "name": [
                "Saban Research Institute, Childrens Hospital Los Angeles, 4650 Sunset Blvd, 90027, Los Angeles, CA, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Gwye", 
            "givenName": "Ynnez", 
            "id": "sg:person.01310250024.26", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01310250024.26"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Saban Research Institute, Childrens Hospital Los Angeles, 4650 Sunset Blvd, 90027, Los Angeles, CA, USA", 
              "id": "http://www.grid.ac/institutes/grid.239546.f", 
              "name": [
                "Saban Research Institute, Childrens Hospital Los Angeles, 4650 Sunset Blvd, 90027, Los Angeles, CA, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Russell", 
            "givenName": "Darren", 
            "id": "sg:person.01271200171.01", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01271200171.01"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Saban Research Institute, Childrens Hospital Los Angeles, 4650 Sunset Blvd, 90027, Los Angeles, CA, USA", 
              "id": "http://www.grid.ac/institutes/grid.239546.f", 
              "name": [
                "Saban Research Institute, Childrens Hospital Los Angeles, 4650 Sunset Blvd, 90027, Los Angeles, CA, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Cao", 
            "givenName": "Christine", 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Saban Research Institute, Childrens Hospital Los Angeles, 4650 Sunset Blvd, 90027, Los Angeles, CA, USA", 
              "id": "http://www.grid.ac/institutes/grid.239546.f", 
              "name": [
                "Saban Research Institute, Childrens Hospital Los Angeles, 4650 Sunset Blvd, 90027, Los Angeles, CA, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Douglas", 
            "givenName": "Dorothea", 
            "id": "sg:person.01215237623.71", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01215237623.71"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Saban Research Institute, Childrens Hospital Los Angeles, 4650 Sunset Blvd, 90027, Los Angeles, CA, USA", 
              "id": "http://www.grid.ac/institutes/grid.239546.f", 
              "name": [
                "Saban Research Institute, Childrens Hospital Los Angeles, 4650 Sunset Blvd, 90027, Los Angeles, CA, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Hung", 
            "givenName": "Long", 
            "id": "sg:person.01232757376.34", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01232757376.34"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Children's Cancer Research Institute, St. Anna Kinderspital, Kinderspitalgasse 6, 1090, Vienna, Austria", 
              "id": "http://www.grid.ac/institutes/grid.416346.2", 
              "name": [
                "Children's Cancer Research Institute, St. Anna Kinderspital, Kinderspitalgasse 6, 1090, Vienna, Austria"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Kovar", 
            "givenName": "Heinrich", 
            "id": "sg:person.0741362200.35", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0741362200.35"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Pathology, Keck School of Medicine, University of Southern California, 90089, Los Angeles, CA, USA", 
              "id": "http://www.grid.ac/institutes/grid.42505.36", 
              "name": [
                "Saban Research Institute, Childrens Hospital Los Angeles, 4650 Sunset Blvd, 90027, Los Angeles, CA, USA", 
                "Pathology, Keck School of Medicine, University of Southern California, 90089, Los Angeles, CA, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Triche", 
            "givenName": "Timothy J", 
            "id": "sg:person.01276675557.65", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01276675557.65"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "University of Michigan, 1150 West Medical Center Drive, 1200 MSRBIII/SPC 5632, 48109-5632, Ann Arbor, MI, USA", 
              "id": "http://www.grid.ac/institutes/grid.214458.e", 
              "name": [
                "Saban Research Institute, Childrens Hospital Los Angeles, 4650 Sunset Blvd, 90027, Los Angeles, CA, USA", 
                "Departments of Pediatrics, University of Southern California, 90089, Los Angeles, CA, USA", 
                "Pathology, Keck School of Medicine, University of Southern California, 90089, Los Angeles, CA, USA", 
                "University of Michigan, 1150 West Medical Center Drive, 1200 MSRBIII/SPC 5632, 48109-5632, Ann Arbor, MI, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Lawlor", 
            "givenName": "Elizabeth R", 
            "id": "sg:person.0742720235.28", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0742720235.28"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "sg:pub.10.1038/sj.onc.1205053", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1009049466", 
              "https://doi.org/10.1038/sj.onc.1205053"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature07567", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1045800863", 
              "https://doi.org/10.1038/nature07567"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/1476-4598-5-67", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1010533206", 
              "https://doi.org/10.1186/1476-4598-5-67"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1201397", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1004676244", 
              "https://doi.org/10.1038/sj.onc.1201397"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature03128", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1027226854", 
              "https://doi.org/10.1038/nature03128"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s00109-008-0357-8", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1015246546", 
              "https://doi.org/10.1007/s00109-008-0357-8"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature05372", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1002972347", 
              "https://doi.org/10.1038/nature05372"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.leu.2404859", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1000158657", 
              "https://doi.org/10.1038/sj.leu.2404859"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nm0797-730", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1022333282", 
              "https://doi.org/10.1038/nm0797-730"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature05236", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1041233330", 
              "https://doi.org/10.1038/nature05236"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1210811", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1022095490", 
              "https://doi.org/10.1038/sj.onc.1210811"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nature04980", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1030873412", 
              "https://doi.org/10.1038/nature04980"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/4351169a", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1009302687", 
              "https://doi.org/10.1038/4351169a"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "2010-03-26", 
        "datePublishedReg": "2010-03-26", 
        "description": "BackgroundSome human cancers demonstrate cellular hierarchies in which tumor-initiating cancer stem cells generate progeny cells with reduced tumorigenic potential. This cancer stem cell population is proposed to be a source of therapy-resistant and recurrent disease. Ewing sarcoma family tumors (ESFT) are highly aggressive cancers in which drug-resistant, relapsed disease remains a significant clinical problem. Recently, the cell surface protein CD133 was identified as a putative marker of tumor-initiating cells in ESFT. We evaluated ESFT tumors and cell lines to determine if high levels of CD133 are associated with drug resistance.MethodsExpression of the CD133-encoding PROM1 gene was determined by RT-PCR in ESFT tumors and cell lines. CD133 protein expression was assessed by western blot, FACS and/or immunostaining. Cell lines were FACS-sorted into CD133+ and CD133- fractions and proliferation, colony formation in soft agar, and in vivo tumorigenicity compared. Chemosensitivity was measured using MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxy-methoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assays.ResultsPROM1 expression was either absent or extremely low in most tumors. However, PROM1 was highly over-expressed in 4 of 48 cases. Two of the 4 patients with PROM1 over-expressing tumors rapidly succumbed to primary drug-resistant disease and two are long-term, event-free survivors. The expression of PROM1 in ESFT cell lines was similarly heterogeneous. The frequency of CD133+ cells ranged from 2-99% and, with one exception, no differences in the chemoresistance or tumorigenicity of CD133+ and CD133- cell fractions were detected. Importantly, however, the STA-ET-8.2 cell line was found to retain a cellular hierarchy in which relatively chemo-resistant, tumorigenic CD133+ cells gave rise to relatively chemo-sensitive, less tumorigenic, CD133- progeny.ConclusionsUp to 10% of ESFT express high levels of PROM1. In some tumors and cell lines the CD133+ fraction is relatively more drug-resistant, while in others there is no apparent difference between CD133+ and CD133- cells. These studies reveal heterogeneity in PROM1/CD133 expression in ESFT tumors and cell lines and confirm that high levels of PROM1 expression are, in at least some cases, associated with chemo-resistant disease. Further studies are required to elucidate the contribution of PROM1/CD133 expressing cells to therapeutic resistance in a large, prospective cohort of primary ESFT.", 
        "genre": "article", 
        "id": "sg:pub.10.1186/1471-2407-10-116", 
        "isAccessibleForFree": true, 
        "isFundedItemOf": [
          {
            "id": "sg:grant.2689067", 
            "type": "MonetaryGrant"
          }
        ], 
        "isPartOf": [
          {
            "id": "sg:journal.1024632", 
            "issn": [
              "1471-2407"
            ], 
            "name": "BMC Cancer", 
            "publisher": "Springer Nature", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "1", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "10"
          }
        ], 
        "keywords": [
          "CD133 expression", 
          "cell lines", 
          "tumor-initiating cancer stem cells", 
          "CD133 protein expression", 
          "frequency of CD133", 
          "event-free survivors", 
          "chemo-resistant disease", 
          "drug-resistant disease", 
          "sarcoma family tumors", 
          "significant clinical problem", 
          "cancer stem cell population", 
          "cell surface protein CD133", 
          "tumor-initiating cells", 
          "cancer stem cells", 
          "ESFT cell lines", 
          "tumorigenic CD133", 
          "recurrent disease", 
          "prospective cohort", 
          "CD133- cell fractions", 
          "Prom1/CD133", 
          "most tumors", 
          "aggressive cancer", 
          "cellular hierarchy", 
          "clinical problem", 
          "tumorigenicity of CD133", 
          "family tumors", 
          "Ewing's sarcoma cells", 
          "PROM1 expression", 
          "therapeutic resistance", 
          "tumors", 
          "high levels", 
          "vivo tumorigenicity", 
          "drug resistance", 
          "CD133", 
          "PROM1 gene", 
          "Western blot", 
          "disease", 
          "MTS assay", 
          "sarcoma cells", 
          "ESFT", 
          "RT-PCR", 
          "protein expression", 
          "putative marker", 
          "PROM1", 
          "human cancers", 
          "colony formation", 
          "tumorigenic potential", 
          "stem cell population", 
          "cell populations", 
          "primary ESFT", 
          "Further studies", 
          "soft agar", 
          "cancer", 
          "stem cells", 
          "tumorigenicity", 
          "cells", 
          "FACS", 
          "expression", 
          "apparent differences", 
          "patients", 
          "MethodsExpression", 
          "chemosensitivity", 
          "cohort", 
          "levels", 
          "chemoresistance", 
          "survivors", 
          "progeny cells", 
          "blot", 
          "differences", 
          "cases", 
          "markers", 
          "proliferation", 
          "ConclusionsUp", 
          "study", 
          "assays", 
          "resistance", 
          "population", 
          "lines", 
          "genes", 
          "fraction", 
          "agar", 
          "heterogeneity", 
          "exception", 
          "frequency", 
          "potential", 
          "rise", 
          "formation", 
          "contribution", 
          "source", 
          "problem", 
          "hierarchy"
        ], 
        "name": "CD133 expression in chemo-resistant Ewing sarcoma cells", 
        "pagination": "116", 
        "productId": [
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1032569982"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1186/1471-2407-10-116"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "20346143"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1186/1471-2407-10-116", 
          "https://app.dimensions.ai/details/publication/pub.1032569982"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2022-08-04T16:58", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-springernature-scigraph/baseset/20220804/entities/gbq_results/article/article_514.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "https://doi.org/10.1186/1471-2407-10-116"
      }
    ]
     

    Download the RDF metadata as:  json-ld nt turtle xml License info

    HOW TO GET THIS DATA PROGRAMMATICALLY:

    JSON-LD is a popular format for linked data which is fully compatible with JSON.

    curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1186/1471-2407-10-116'

    N-Triples is a line-based linked data format ideal for batch operations.

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1186/1471-2407-10-116'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1186/1471-2407-10-116'

    RDF/XML is a standard XML format for linked data.

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1186/1471-2407-10-116'


     

    This table displays all metadata directly associated to this object as RDF triples.

    341 TRIPLES      21 PREDICATES      146 URIs      125 LITERALS      24 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1186/1471-2407-10-116 schema:about N03c7f8a783e240b5ba05069e149ba840
    2 N2d2cbfa9390145a18e0fec8db796826d
    3 N3ed81c29d88d42798cc845175d471a7c
    4 N3fe62b46f44041ef918a8a878ee44271
    5 N47589db834084d40b715305cdd041b6c
    6 N527bf2bad7c04638a1fee264f116eded
    7 N59ea6f20a49f4a38b26cbeecd44f7dac
    8 N66d0ac1fe3224370917a29a38f589524
    9 N6a9e8963a8324619bbd3bfaf21274d73
    10 N776b2b8bd4cd4221809ce5e7a7fb6b56
    11 N7a2f4fe39ed547ee9f557226b1d5558e
    12 N95c06966915646dda09569e04a16f8c9
    13 N96c4b031abb745748c2e5ce8ba6d0e74
    14 Na124dcf98c5c49d2a962bf09ceb61125
    15 Nb213117144e44be0b456cfa3c29c7167
    16 Nb4ee5d4755b440fb8857aff265bb908b
    17 Ne565f162753c4fe697b94e3d46744f2c
    18 anzsrc-for:11
    19 anzsrc-for:1112
    20 schema:author Ne11f6ef5dafd41cc898085695b377c03
    21 schema:citation sg:pub.10.1007/s00109-008-0357-8
    22 sg:pub.10.1038/4351169a
    23 sg:pub.10.1038/nature03128
    24 sg:pub.10.1038/nature04980
    25 sg:pub.10.1038/nature05236
    26 sg:pub.10.1038/nature05372
    27 sg:pub.10.1038/nature07567
    28 sg:pub.10.1038/nm0797-730
    29 sg:pub.10.1038/sj.leu.2404859
    30 sg:pub.10.1038/sj.onc.1201397
    31 sg:pub.10.1038/sj.onc.1205053
    32 sg:pub.10.1038/sj.onc.1210811
    33 sg:pub.10.1186/1476-4598-5-67
    34 schema:datePublished 2010-03-26
    35 schema:datePublishedReg 2010-03-26
    36 schema:description BackgroundSome human cancers demonstrate cellular hierarchies in which tumor-initiating cancer stem cells generate progeny cells with reduced tumorigenic potential. This cancer stem cell population is proposed to be a source of therapy-resistant and recurrent disease. Ewing sarcoma family tumors (ESFT) are highly aggressive cancers in which drug-resistant, relapsed disease remains a significant clinical problem. Recently, the cell surface protein CD133 was identified as a putative marker of tumor-initiating cells in ESFT. We evaluated ESFT tumors and cell lines to determine if high levels of CD133 are associated with drug resistance.MethodsExpression of the CD133-encoding PROM1 gene was determined by RT-PCR in ESFT tumors and cell lines. CD133 protein expression was assessed by western blot, FACS and/or immunostaining. Cell lines were FACS-sorted into CD133+ and CD133- fractions and proliferation, colony formation in soft agar, and in vivo tumorigenicity compared. Chemosensitivity was measured using MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxy-methoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assays.ResultsPROM1 expression was either absent or extremely low in most tumors. However, PROM1 was highly over-expressed in 4 of 48 cases. Two of the 4 patients with PROM1 over-expressing tumors rapidly succumbed to primary drug-resistant disease and two are long-term, event-free survivors. The expression of PROM1 in ESFT cell lines was similarly heterogeneous. The frequency of CD133+ cells ranged from 2-99% and, with one exception, no differences in the chemoresistance or tumorigenicity of CD133+ and CD133- cell fractions were detected. Importantly, however, the STA-ET-8.2 cell line was found to retain a cellular hierarchy in which relatively chemo-resistant, tumorigenic CD133+ cells gave rise to relatively chemo-sensitive, less tumorigenic, CD133- progeny.ConclusionsUp to 10% of ESFT express high levels of PROM1. In some tumors and cell lines the CD133+ fraction is relatively more drug-resistant, while in others there is no apparent difference between CD133+ and CD133- cells. These studies reveal heterogeneity in PROM1/CD133 expression in ESFT tumors and cell lines and confirm that high levels of PROM1 expression are, in at least some cases, associated with chemo-resistant disease. Further studies are required to elucidate the contribution of PROM1/CD133 expressing cells to therapeutic resistance in a large, prospective cohort of primary ESFT.
    37 schema:genre article
    38 schema:isAccessibleForFree true
    39 schema:isPartOf N181bd4371a4842d4ab34971132a2956f
    40 N97198c77cce34af5977c7c5adcc10808
    41 sg:journal.1024632
    42 schema:keywords CD133
    43 CD133 expression
    44 CD133 protein expression
    45 CD133- cell fractions
    46 ConclusionsUp
    47 ESFT
    48 ESFT cell lines
    49 Ewing's sarcoma cells
    50 FACS
    51 Further studies
    52 MTS assay
    53 MethodsExpression
    54 PROM1
    55 PROM1 expression
    56 PROM1 gene
    57 Prom1/CD133
    58 RT-PCR
    59 Western blot
    60 agar
    61 aggressive cancer
    62 apparent differences
    63 assays
    64 blot
    65 cancer
    66 cancer stem cell population
    67 cancer stem cells
    68 cases
    69 cell lines
    70 cell populations
    71 cell surface protein CD133
    72 cells
    73 cellular hierarchy
    74 chemo-resistant disease
    75 chemoresistance
    76 chemosensitivity
    77 clinical problem
    78 cohort
    79 colony formation
    80 contribution
    81 differences
    82 disease
    83 drug resistance
    84 drug-resistant disease
    85 event-free survivors
    86 exception
    87 expression
    88 family tumors
    89 formation
    90 fraction
    91 frequency
    92 frequency of CD133
    93 genes
    94 heterogeneity
    95 hierarchy
    96 high levels
    97 human cancers
    98 levels
    99 lines
    100 markers
    101 most tumors
    102 patients
    103 population
    104 potential
    105 primary ESFT
    106 problem
    107 progeny cells
    108 proliferation
    109 prospective cohort
    110 protein expression
    111 putative marker
    112 recurrent disease
    113 resistance
    114 rise
    115 sarcoma cells
    116 sarcoma family tumors
    117 significant clinical problem
    118 soft agar
    119 source
    120 stem cell population
    121 stem cells
    122 study
    123 survivors
    124 therapeutic resistance
    125 tumor-initiating cancer stem cells
    126 tumor-initiating cells
    127 tumorigenic CD133
    128 tumorigenic potential
    129 tumorigenicity
    130 tumorigenicity of CD133
    131 tumors
    132 vivo tumorigenicity
    133 schema:name CD133 expression in chemo-resistant Ewing sarcoma cells
    134 schema:pagination 116
    135 schema:productId N1e4ae1ac45a24f998723240404de5d7e
    136 N3b32e0d745fc448bba35518a07db4f96
    137 Nca6e685b6f8c4dc4a200d11f4197ca38
    138 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032569982
    139 https://doi.org/10.1186/1471-2407-10-116
    140 schema:sdDatePublished 2022-08-04T16:58
    141 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    142 schema:sdPublisher Nea0eea33a4d5444288e2326dcbb75662
    143 schema:url https://doi.org/10.1186/1471-2407-10-116
    144 sgo:license sg:explorer/license/
    145 sgo:sdDataset articles
    146 rdf:type schema:ScholarlyArticle
    147 N03c7f8a783e240b5ba05069e149ba840 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    148 schema:name Cell Separation
    149 rdf:type schema:DefinedTerm
    150 N1671fc394f1c49a3b971b1616d1fcf31 schema:affiliation grid-institutes:grid.239546.f
    151 schema:familyName Cao
    152 schema:givenName Christine
    153 rdf:type schema:Person
    154 N181bd4371a4842d4ab34971132a2956f schema:issueNumber 1
    155 rdf:type schema:PublicationIssue
    156 N1e4ae1ac45a24f998723240404de5d7e schema:name doi
    157 schema:value 10.1186/1471-2407-10-116
    158 rdf:type schema:PropertyValue
    159 N2d2cbfa9390145a18e0fec8db796826d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    160 schema:name Mice, Inbred NOD
    161 rdf:type schema:DefinedTerm
    162 N3b32e0d745fc448bba35518a07db4f96 schema:name pubmed_id
    163 schema:value 20346143
    164 rdf:type schema:PropertyValue
    165 N3ed81c29d88d42798cc845175d471a7c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    166 schema:name Mice, SCID
    167 rdf:type schema:DefinedTerm
    168 N3f329fc1bc7c4dcab15648317025c066 rdf:first sg:person.0741362200.35
    169 rdf:rest N9a3b7d680fa14a5c976a9f319f45fe8a
    170 N3fe62b46f44041ef918a8a878ee44271 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    171 schema:name Flow Cytometry
    172 rdf:type schema:DefinedTerm
    173 N47589db834084d40b715305cdd041b6c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    174 schema:name Humans
    175 rdf:type schema:DefinedTerm
    176 N4ac735b3c79b4729abc906e003f4589f rdf:first N1671fc394f1c49a3b971b1616d1fcf31
    177 rdf:rest Nebc6a980918343aa80cecab8a4db62be
    178 N527bf2bad7c04638a1fee264f116eded schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    179 schema:name Antigens, CD
    180 rdf:type schema:DefinedTerm
    181 N59ea6f20a49f4a38b26cbeecd44f7dac schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    182 schema:name AC133 Antigen
    183 rdf:type schema:DefinedTerm
    184 N6484ba79531f4229b7f8273fa603ac2d rdf:first sg:person.01232757376.34
    185 rdf:rest N3f329fc1bc7c4dcab15648317025c066
    186 N66d0ac1fe3224370917a29a38f589524 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    187 schema:name Cohort Studies
    188 rdf:type schema:DefinedTerm
    189 N6a9e8963a8324619bbd3bfaf21274d73 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    190 schema:name Recurrence
    191 rdf:type schema:DefinedTerm
    192 N6eceef11f4724237a885865afd31be2d rdf:first sg:person.0742720235.28
    193 rdf:rest rdf:nil
    194 N776b2b8bd4cd4221809ce5e7a7fb6b56 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    195 schema:name Peptides
    196 rdf:type schema:DefinedTerm
    197 N7a2f4fe39ed547ee9f557226b1d5558e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    198 schema:name Animals
    199 rdf:type schema:DefinedTerm
    200 N95c06966915646dda09569e04a16f8c9 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    201 schema:name Drug Resistance, Neoplasm
    202 rdf:type schema:DefinedTerm
    203 N96c4b031abb745748c2e5ce8ba6d0e74 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    204 schema:name Reverse Transcriptase Polymerase Chain Reaction
    205 rdf:type schema:DefinedTerm
    206 N97198c77cce34af5977c7c5adcc10808 schema:volumeNumber 10
    207 rdf:type schema:PublicationVolume
    208 N9a3b7d680fa14a5c976a9f319f45fe8a rdf:first sg:person.01276675557.65
    209 rdf:rest N6eceef11f4724237a885865afd31be2d
    210 Na124dcf98c5c49d2a962bf09ceb61125 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    211 schema:name Mice
    212 rdf:type schema:DefinedTerm
    213 Nb213117144e44be0b456cfa3c29c7167 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    214 schema:name Gene Expression Regulation, Neoplastic
    215 rdf:type schema:DefinedTerm
    216 Nb4ee5d4755b440fb8857aff265bb908b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    217 schema:name Glycoproteins
    218 rdf:type schema:DefinedTerm
    219 Nca6e685b6f8c4dc4a200d11f4197ca38 schema:name dimensions_id
    220 schema:value pub.1032569982
    221 rdf:type schema:PropertyValue
    222 Ndd175363a8334f8fb28533fc9242f6d8 rdf:first sg:person.01271200171.01
    223 rdf:rest N4ac735b3c79b4729abc906e003f4589f
    224 Ne11f6ef5dafd41cc898085695b377c03 rdf:first sg:person.01207627037.15
    225 rdf:rest Ne352ed2629364bcaaaefa6d1198f3508
    226 Ne352ed2629364bcaaaefa6d1198f3508 rdf:first sg:person.01310250024.26
    227 rdf:rest Ndd175363a8334f8fb28533fc9242f6d8
    228 Ne565f162753c4fe697b94e3d46744f2c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    229 schema:name Sarcoma, Ewing
    230 rdf:type schema:DefinedTerm
    231 Nea0eea33a4d5444288e2326dcbb75662 schema:name Springer Nature - SN SciGraph project
    232 rdf:type schema:Organization
    233 Nebc6a980918343aa80cecab8a4db62be rdf:first sg:person.01215237623.71
    234 rdf:rest N6484ba79531f4229b7f8273fa603ac2d
    235 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
    236 schema:name Medical and Health Sciences
    237 rdf:type schema:DefinedTerm
    238 anzsrc-for:1112 schema:inDefinedTermSet anzsrc-for:
    239 schema:name Oncology and Carcinogenesis
    240 rdf:type schema:DefinedTerm
    241 sg:grant.2689067 http://pending.schema.org/fundedItem sg:pub.10.1186/1471-2407-10-116
    242 rdf:type schema:MonetaryGrant
    243 sg:journal.1024632 schema:issn 1471-2407
    244 schema:name BMC Cancer
    245 schema:publisher Springer Nature
    246 rdf:type schema:Periodical
    247 sg:person.01207627037.15 schema:affiliation grid-institutes:grid.239546.f
    248 schema:familyName Jiang
    249 schema:givenName Xiaohua
    250 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01207627037.15
    251 rdf:type schema:Person
    252 sg:person.01215237623.71 schema:affiliation grid-institutes:grid.239546.f
    253 schema:familyName Douglas
    254 schema:givenName Dorothea
    255 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01215237623.71
    256 rdf:type schema:Person
    257 sg:person.01232757376.34 schema:affiliation grid-institutes:grid.239546.f
    258 schema:familyName Hung
    259 schema:givenName Long
    260 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01232757376.34
    261 rdf:type schema:Person
    262 sg:person.01271200171.01 schema:affiliation grid-institutes:grid.239546.f
    263 schema:familyName Russell
    264 schema:givenName Darren
    265 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01271200171.01
    266 rdf:type schema:Person
    267 sg:person.01276675557.65 schema:affiliation grid-institutes:grid.42505.36
    268 schema:familyName Triche
    269 schema:givenName Timothy J
    270 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01276675557.65
    271 rdf:type schema:Person
    272 sg:person.01310250024.26 schema:affiliation grid-institutes:grid.239546.f
    273 schema:familyName Gwye
    274 schema:givenName Ynnez
    275 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01310250024.26
    276 rdf:type schema:Person
    277 sg:person.0741362200.35 schema:affiliation grid-institutes:grid.416346.2
    278 schema:familyName Kovar
    279 schema:givenName Heinrich
    280 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0741362200.35
    281 rdf:type schema:Person
    282 sg:person.0742720235.28 schema:affiliation grid-institutes:grid.214458.e
    283 schema:familyName Lawlor
    284 schema:givenName Elizabeth R
    285 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0742720235.28
    286 rdf:type schema:Person
    287 sg:pub.10.1007/s00109-008-0357-8 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015246546
    288 https://doi.org/10.1007/s00109-008-0357-8
    289 rdf:type schema:CreativeWork
    290 sg:pub.10.1038/4351169a schema:sameAs https://app.dimensions.ai/details/publication/pub.1009302687
    291 https://doi.org/10.1038/4351169a
    292 rdf:type schema:CreativeWork
    293 sg:pub.10.1038/nature03128 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027226854
    294 https://doi.org/10.1038/nature03128
    295 rdf:type schema:CreativeWork
    296 sg:pub.10.1038/nature04980 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030873412
    297 https://doi.org/10.1038/nature04980
    298 rdf:type schema:CreativeWork
    299 sg:pub.10.1038/nature05236 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041233330
    300 https://doi.org/10.1038/nature05236
    301 rdf:type schema:CreativeWork
    302 sg:pub.10.1038/nature05372 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002972347
    303 https://doi.org/10.1038/nature05372
    304 rdf:type schema:CreativeWork
    305 sg:pub.10.1038/nature07567 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045800863
    306 https://doi.org/10.1038/nature07567
    307 rdf:type schema:CreativeWork
    308 sg:pub.10.1038/nm0797-730 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022333282
    309 https://doi.org/10.1038/nm0797-730
    310 rdf:type schema:CreativeWork
    311 sg:pub.10.1038/sj.leu.2404859 schema:sameAs https://app.dimensions.ai/details/publication/pub.1000158657
    312 https://doi.org/10.1038/sj.leu.2404859
    313 rdf:type schema:CreativeWork
    314 sg:pub.10.1038/sj.onc.1201397 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004676244
    315 https://doi.org/10.1038/sj.onc.1201397
    316 rdf:type schema:CreativeWork
    317 sg:pub.10.1038/sj.onc.1205053 schema:sameAs https://app.dimensions.ai/details/publication/pub.1009049466
    318 https://doi.org/10.1038/sj.onc.1205053
    319 rdf:type schema:CreativeWork
    320 sg:pub.10.1038/sj.onc.1210811 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022095490
    321 https://doi.org/10.1038/sj.onc.1210811
    322 rdf:type schema:CreativeWork
    323 sg:pub.10.1186/1476-4598-5-67 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010533206
    324 https://doi.org/10.1186/1476-4598-5-67
    325 rdf:type schema:CreativeWork
    326 grid-institutes:grid.214458.e schema:alternateName University of Michigan, 1150 West Medical Center Drive, 1200 MSRBIII/SPC 5632, 48109-5632, Ann Arbor, MI, USA
    327 schema:name Departments of Pediatrics, University of Southern California, 90089, Los Angeles, CA, USA
    328 Pathology, Keck School of Medicine, University of Southern California, 90089, Los Angeles, CA, USA
    329 Saban Research Institute, Childrens Hospital Los Angeles, 4650 Sunset Blvd, 90027, Los Angeles, CA, USA
    330 University of Michigan, 1150 West Medical Center Drive, 1200 MSRBIII/SPC 5632, 48109-5632, Ann Arbor, MI, USA
    331 rdf:type schema:Organization
    332 grid-institutes:grid.239546.f schema:alternateName Saban Research Institute, Childrens Hospital Los Angeles, 4650 Sunset Blvd, 90027, Los Angeles, CA, USA
    333 schema:name Saban Research Institute, Childrens Hospital Los Angeles, 4650 Sunset Blvd, 90027, Los Angeles, CA, USA
    334 rdf:type schema:Organization
    335 grid-institutes:grid.416346.2 schema:alternateName Children's Cancer Research Institute, St. Anna Kinderspital, Kinderspitalgasse 6, 1090, Vienna, Austria
    336 schema:name Children's Cancer Research Institute, St. Anna Kinderspital, Kinderspitalgasse 6, 1090, Vienna, Austria
    337 rdf:type schema:Organization
    338 grid-institutes:grid.42505.36 schema:alternateName Pathology, Keck School of Medicine, University of Southern California, 90089, Los Angeles, CA, USA
    339 schema:name Pathology, Keck School of Medicine, University of Southern California, 90089, Los Angeles, CA, USA
    340 Saban Research Institute, Childrens Hospital Los Angeles, 4650 Sunset Blvd, 90027, Los Angeles, CA, USA
    341 rdf:type schema:Organization
     




    Preview window. Press ESC to close (or click here)


    ...