New model of tumor angiogenesis: dynamic balance between vessel regression and growth mediated by angiopoietins and VEGF View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

1999-09

AUTHORS

J Holash, S J Wiegand, G D Yancopoulos

ABSTRACT

Our analyses in several different tumor settings challenge the prevailing view that malignancies and metastases generally initiate as avascular masses that only belatedly induce vascular support. Instead, we find that malignant cells rapidly co-opt existing host vessels to form an initially well-vascularized tumor mass. Paradoxically, the co-opted vasculature does not undergo angiogenesis to support the growing tumor, but instead regresses (perhaps as part of a normal host defense mechanism) via a process that involves disruption of endothelial cell/smooth muscle cell interactions and endothelial cell apoptosis. This vessel regression in turn results in necrosis within the central part of the tumor. However, robust angiogenesis is initiated at the tumor margin, rescuing the surviving tumor and supporting further growth. The expression patterns of Angiopoietin-2 (the natural antagonist for the angiogenic Tie2 receptor) and vascular endothelial growth factor (VEGF) strongly implicate these factors in the above processes. Angiopoietin-2 is highly induced in co-opted vessels, prior to VEGF induction in the adjacent tumor cells, providing perhaps the earliest marker of tumor vasculature and apparently marking the co-opted vessels for regression. Subsequently, VEGF upregulation coincident with Angiopoietin-2 expression at the tumor periphery is associated with robust angiogenesis. Thus, in tumors, Angiopoietin-2 and VEGF seem to reprise the roles they play during vascular remodeling in normal tissues, acting to regulate the previously underappreciated balance between vascular regression and growth. More... »

PAGES

1203035

Journal

TITLE

Oncogene

ISSUE

38

VOLUME

18

Author Affiliations

Related Patents

  • Antibodies Directed To Angiopoietin-2 And Uses Thereof
  • Methods For Increasing Capillary Density And Maintaining Viability Of Microvascular Cardiac Endothelial Cells Using Trk Receptor Ligands
  • Stabilized Angiopoietin-2 Antibodies And Uses Thereof
  • Inhibitors Of Angiopoietin-Like 4 Protein, Combinations, And Their Use
  • Treating Macular Degeneration Using Antibodies To Aminophospholipids
  • Targeting And Imaging Tumor Vasculature Using Conjugates That Bind To Aminophospholipids
  • Treatment Protocol Generation For Diseases Related To Angiogenesis
  • Oncolytic Adenovirus Armed With Therapeutic Genes
  • Vascular Endothelial Cell Growth Inhibitor, Vegi-192a
  • Cancer Treatment Kits Comprising Therapeutic Antibody Conjugates That Bind To Aminophospholipids
  • Targeted Treatment Of Anerobic Cancer
  • Combined Methods For Tumor Coagulation And Tumor Treatment
  • Cancer Treatment Kits Using Antibodies To Aminophospholipids
  • Antibodies Directed To Angiopoietin-2 And Uses Thereof
  • Vascular Endothelial Cell Growth Inhibitor, Vegi-192a
  • Antibodies Directed To Angiopoietin-2 And Uses Thereof
  • Methods And Pharmaceuticals Compositions For Treating Coronary Artery Disease, Ischemia,And Vascular Disease Using Angiopoietins
  • Oncolytic Adenovirus Armed With Therapeutic Genes
  • Inhibitors Of Angiopoietin-Like 4 Protein, Combinations, And Their Use
  • Methods For Increasing Vascular Density And Maintaining Viability Of Microvascular Endothelial Cells Using Trk Receptor Ligands
  • Compositions And Methods For The Diagnosis And Treatment Of Tumor
  • Targeted Treatment Of Anerobic Cancer
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/sj.onc.1203035

    DOI

    http://dx.doi.org/10.1038/sj.onc.1203035

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1043078580

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/10498889


    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/2008/0601", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Biochemistry and Cell Biology", 
            "type": "DefinedTerm"
          }, 
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/06", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Biological Sciences", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Angiopoietin-1", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Angiopoietin-2", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Animals", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Blood Vessels", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Endothelial Growth Factors", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Humans", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Lymphokines", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Membrane Glycoproteins", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Models, Biological", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Neoplasms", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Neovascularization, Pathologic", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Proteins", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Vascular Endothelial Growth Factor A", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Vascular Endothelial Growth Factors", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "Regeneron (United States)", 
              "id": "https://www.grid.ac/institutes/grid.418961.3", 
              "name": [
                "Regeneron Pharmaceuticals, Inc., 777 Old Saw Mill River Road, Tarrytown, New York, NY 10591, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Holash", 
            "givenName": "J", 
            "id": "sg:person.0701501306.40", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0701501306.40"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Regeneron (United States)", 
              "id": "https://www.grid.ac/institutes/grid.418961.3", 
              "name": [
                "Regeneron Pharmaceuticals, Inc., 777 Old Saw Mill River Road, Tarrytown, New York, NY 10591, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Wiegand", 
            "givenName": "S J", 
            "id": "sg:person.01233506031.30", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01233506031.30"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Regeneron (United States)", 
              "id": "https://www.grid.ac/institutes/grid.418961.3", 
              "name": [
                "Regeneron Pharmaceuticals, Inc., 777 Old Saw Mill River Road, Tarrytown, New York, NY 10591, USA"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Yancopoulos", 
            "givenName": "G D", 
            "id": "sg:person.01274702531.47", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01274702531.47"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "https://doi.org/10.1073/pnas.95.15.8829", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1003453811"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/380439a0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1004384986", 
              "https://doi.org/10.1038/380439a0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1073/pnas.92.3.768", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1006823065"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/bf00334878", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1009431133", 
              "https://doi.org/10.1007/bf00334878"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1101/gad.8.16.1897", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1009594234"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1201090", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1009788098", 
              "https://doi.org/10.1038/sj.onc.1201090"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1201090", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1009788098", 
              "https://doi.org/10.1038/sj.onc.1201090"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s0002-9440(10)65733-1", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1012260400"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s0092-8674(00)81813-9", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1012641956"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/362841a0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1013132150", 
              "https://doi.org/10.1038/362841a0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/367576a0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1016282476", 
              "https://doi.org/10.1038/367576a0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s0092-8674(00)81812-7", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1020325309"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/376062a0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1021421211", 
              "https://doi.org/10.1038/376062a0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1172/jci5028", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1022103776"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s0092-8674(00)81810-3", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1023164650"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/978-3-642-59953-8_1", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1023492449", 
              "https://doi.org/10.1007/978-3-642-59953-8_1"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/978-3-642-59953-8_1", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1023492449", 
              "https://doi.org/10.1007/978-3-642-59953-8_1"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1172/jci117857", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1024866358"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nm0295-149", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1025343841", 
              "https://doi.org/10.1038/nm0295-149"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1056/nejm197111182852108", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1031952402"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/376070a0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1033168641", 
              "https://doi.org/10.1038/376070a0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/380435a0", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1034005847", 
              "https://doi.org/10.1038/380435a0"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s0014-5793(99)00378-6", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1034707757"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1073/pnas.95.15.8795", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1037720209"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/s0092-8674(00)80108-7", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1042440169"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1056/nejm197108122850711", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1042994614"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1172/jci119740", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1045876259"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1093/jnci/82.1.4", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1051237830"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1126/science.277.5322.55", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1062557236"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1126/science.282.5388.468", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1062562857"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1126/science.284.5422.1994", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1062565623"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1161/01.res.81.4.567", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1063341158"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.3171/jns.1994.81.6.0902", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1071097435"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.3171/jns.1994.81.6.0902", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1071097435"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.3171/jns.1994.81.6.0902", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1071097435"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1074261048", 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1082424606", 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1082876818", 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1083169022", 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "1999-09", 
        "datePublishedReg": "1999-09-01", 
        "description": "Our analyses in several different tumor settings challenge the prevailing view that malignancies and metastases generally initiate as avascular masses that only belatedly induce vascular support. Instead, we find that malignant cells rapidly co-opt existing host vessels to form an initially well-vascularized tumor mass. Paradoxically, the co-opted vasculature does not undergo angiogenesis to support the growing tumor, but instead regresses (perhaps as part of a normal host defense mechanism) via a process that involves disruption of endothelial cell/smooth muscle cell interactions and endothelial cell apoptosis. This vessel regression in turn results in necrosis within the central part of the tumor. However, robust angiogenesis is initiated at the tumor margin, rescuing the surviving tumor and supporting further growth. The expression patterns of Angiopoietin-2 (the natural antagonist for the angiogenic Tie2 receptor) and vascular endothelial growth factor (VEGF) strongly implicate these factors in the above processes. Angiopoietin-2 is highly induced in co-opted vessels, prior to VEGF induction in the adjacent tumor cells, providing perhaps the earliest marker of tumor vasculature and apparently marking the co-opted vessels for regression. Subsequently, VEGF upregulation coincident with Angiopoietin-2 expression at the tumor periphery is associated with robust angiogenesis. Thus, in tumors, Angiopoietin-2 and VEGF seem to reprise the roles they play during vascular remodeling in normal tissues, acting to regulate the previously underappreciated balance between vascular regression and growth.", 
        "genre": "research_article", 
        "id": "sg:pub.10.1038/sj.onc.1203035", 
        "inLanguage": [
          "en"
        ], 
        "isAccessibleForFree": true, 
        "isPartOf": [
          {
            "id": "sg:journal.1097543", 
            "issn": [
              "0950-9232", 
              "1476-5594"
            ], 
            "name": "Oncogene", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "38", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "18"
          }
        ], 
        "name": "New model of tumor angiogenesis: dynamic balance between vessel regression and growth mediated by angiopoietins and VEGF", 
        "pagination": "1203035", 
        "productId": [
          {
            "name": "readcube_id", 
            "type": "PropertyValue", 
            "value": [
              "cd32cd23f36ef62aab45fe984efc317217ba0d63b6df266056328f293a1a7263"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "10498889"
            ]
          }, 
          {
            "name": "nlm_unique_id", 
            "type": "PropertyValue", 
            "value": [
              "8711562"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1038/sj.onc.1203035"
            ]
          }, 
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1043078580"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1038/sj.onc.1203035", 
          "https://app.dimensions.ai/details/publication/pub.1043078580"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2019-04-11T11:57", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000359_0000000359/records_29219_00000002.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "http://www.nature.com/articles/1203035"
      }
    ]
     

    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.10.1038/sj.onc.1203035'

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

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/sj.onc.1203035'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/sj.onc.1203035'

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

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/sj.onc.1203035'


     

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

    250 TRIPLES      21 PREDICATES      78 URIs      35 LITERALS      23 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1038/sj.onc.1203035 schema:about N01788a911ec3440985c6d8bb236ff728
    2 N0998d84fe7e642fcb53b2f39cfb256d1
    3 N268098508ff145cba38f0a8b0ec7ad0e
    4 N3c73d9d225704ebcad9db0cb54f24fbc
    5 N49789c0ec4374afc8a2dbc76eb15e0e9
    6 N4c204ba6b92641039c07adbd6fe08757
    7 N890b612be8eb46b99692f75a1d1a290c
    8 N9951d1b6c8d148eb87591817ed68bccc
    9 Na9f97754c9d84c2dbed850a6b6d04109
    10 Naf42731b36cd4900b761e067250b07f3
    11 Nb0738ce4633540b89e3ed7a39caa3d65
    12 Nba5a909ba53e428a8f57de8ff9bd0b5c
    13 Nbc4459251f104fdb82bea24ed064e82a
    14 Nc2129a9eb40c4076921f4f557a0405c5
    15 anzsrc-for:06
    16 anzsrc-for:0601
    17 schema:author N1a1378b4a3ae4f608aa65322908e5699
    18 schema:citation sg:pub.10.1007/978-3-642-59953-8_1
    19 sg:pub.10.1007/bf00334878
    20 sg:pub.10.1038/362841a0
    21 sg:pub.10.1038/367576a0
    22 sg:pub.10.1038/376062a0
    23 sg:pub.10.1038/376070a0
    24 sg:pub.10.1038/380435a0
    25 sg:pub.10.1038/380439a0
    26 sg:pub.10.1038/nm0295-149
    27 sg:pub.10.1038/sj.onc.1201090
    28 https://app.dimensions.ai/details/publication/pub.1074261048
    29 https://app.dimensions.ai/details/publication/pub.1082424606
    30 https://app.dimensions.ai/details/publication/pub.1082876818
    31 https://app.dimensions.ai/details/publication/pub.1083169022
    32 https://doi.org/10.1016/s0002-9440(10)65733-1
    33 https://doi.org/10.1016/s0014-5793(99)00378-6
    34 https://doi.org/10.1016/s0092-8674(00)80108-7
    35 https://doi.org/10.1016/s0092-8674(00)81810-3
    36 https://doi.org/10.1016/s0092-8674(00)81812-7
    37 https://doi.org/10.1016/s0092-8674(00)81813-9
    38 https://doi.org/10.1056/nejm197108122850711
    39 https://doi.org/10.1056/nejm197111182852108
    40 https://doi.org/10.1073/pnas.92.3.768
    41 https://doi.org/10.1073/pnas.95.15.8795
    42 https://doi.org/10.1073/pnas.95.15.8829
    43 https://doi.org/10.1093/jnci/82.1.4
    44 https://doi.org/10.1101/gad.8.16.1897
    45 https://doi.org/10.1126/science.277.5322.55
    46 https://doi.org/10.1126/science.282.5388.468
    47 https://doi.org/10.1126/science.284.5422.1994
    48 https://doi.org/10.1161/01.res.81.4.567
    49 https://doi.org/10.1172/jci117857
    50 https://doi.org/10.1172/jci119740
    51 https://doi.org/10.1172/jci5028
    52 https://doi.org/10.3171/jns.1994.81.6.0902
    53 schema:datePublished 1999-09
    54 schema:datePublishedReg 1999-09-01
    55 schema:description Our analyses in several different tumor settings challenge the prevailing view that malignancies and metastases generally initiate as avascular masses that only belatedly induce vascular support. Instead, we find that malignant cells rapidly co-opt existing host vessels to form an initially well-vascularized tumor mass. Paradoxically, the co-opted vasculature does not undergo angiogenesis to support the growing tumor, but instead regresses (perhaps as part of a normal host defense mechanism) via a process that involves disruption of endothelial cell/smooth muscle cell interactions and endothelial cell apoptosis. This vessel regression in turn results in necrosis within the central part of the tumor. However, robust angiogenesis is initiated at the tumor margin, rescuing the surviving tumor and supporting further growth. The expression patterns of Angiopoietin-2 (the natural antagonist for the angiogenic Tie2 receptor) and vascular endothelial growth factor (VEGF) strongly implicate these factors in the above processes. Angiopoietin-2 is highly induced in co-opted vessels, prior to VEGF induction in the adjacent tumor cells, providing perhaps the earliest marker of tumor vasculature and apparently marking the co-opted vessels for regression. Subsequently, VEGF upregulation coincident with Angiopoietin-2 expression at the tumor periphery is associated with robust angiogenesis. Thus, in tumors, Angiopoietin-2 and VEGF seem to reprise the roles they play during vascular remodeling in normal tissues, acting to regulate the previously underappreciated balance between vascular regression and growth.
    56 schema:genre research_article
    57 schema:inLanguage en
    58 schema:isAccessibleForFree true
    59 schema:isPartOf N0d1fa951297046a6960bd23922c47f70
    60 N409d47175ab2463182423fac19d808ed
    61 sg:journal.1097543
    62 schema:name New model of tumor angiogenesis: dynamic balance between vessel regression and growth mediated by angiopoietins and VEGF
    63 schema:pagination 1203035
    64 schema:productId N1e7f3c999ef84d86b9212c1ae99141b4
    65 N2db49a3e148149cfa9b3dfda16ede8f5
    66 N6db7a05b06ea44c093432a10b0ebbd05
    67 N78bbed74cb674babb078b0f64e189dfe
    68 N9f40633734534291a72bcd51d627162c
    69 schema:sameAs https://app.dimensions.ai/details/publication/pub.1043078580
    70 https://doi.org/10.1038/sj.onc.1203035
    71 schema:sdDatePublished 2019-04-11T11:57
    72 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    73 schema:sdPublisher Nf358e85c420c4c68ab96e3d864c959c1
    74 schema:url http://www.nature.com/articles/1203035
    75 sgo:license sg:explorer/license/
    76 sgo:sdDataset articles
    77 rdf:type schema:ScholarlyArticle
    78 N01788a911ec3440985c6d8bb236ff728 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    79 schema:name Proteins
    80 rdf:type schema:DefinedTerm
    81 N0998d84fe7e642fcb53b2f39cfb256d1 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    82 schema:name Blood Vessels
    83 rdf:type schema:DefinedTerm
    84 N0d1fa951297046a6960bd23922c47f70 schema:volumeNumber 18
    85 rdf:type schema:PublicationVolume
    86 N1a1378b4a3ae4f608aa65322908e5699 rdf:first sg:person.0701501306.40
    87 rdf:rest Nec16a6f95df741caa274a295d63e44b2
    88 N1e7f3c999ef84d86b9212c1ae99141b4 schema:name dimensions_id
    89 schema:value pub.1043078580
    90 rdf:type schema:PropertyValue
    91 N268098508ff145cba38f0a8b0ec7ad0e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    92 schema:name Humans
    93 rdf:type schema:DefinedTerm
    94 N2db49a3e148149cfa9b3dfda16ede8f5 schema:name nlm_unique_id
    95 schema:value 8711562
    96 rdf:type schema:PropertyValue
    97 N3c73d9d225704ebcad9db0cb54f24fbc schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    98 schema:name Vascular Endothelial Growth Factors
    99 rdf:type schema:DefinedTerm
    100 N409d47175ab2463182423fac19d808ed schema:issueNumber 38
    101 rdf:type schema:PublicationIssue
    102 N49789c0ec4374afc8a2dbc76eb15e0e9 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    103 schema:name Neovascularization, Pathologic
    104 rdf:type schema:DefinedTerm
    105 N4c204ba6b92641039c07adbd6fe08757 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    106 schema:name Neoplasms
    107 rdf:type schema:DefinedTerm
    108 N6db7a05b06ea44c093432a10b0ebbd05 schema:name doi
    109 schema:value 10.1038/sj.onc.1203035
    110 rdf:type schema:PropertyValue
    111 N78bbed74cb674babb078b0f64e189dfe schema:name pubmed_id
    112 schema:value 10498889
    113 rdf:type schema:PropertyValue
    114 N890b612be8eb46b99692f75a1d1a290c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    115 schema:name Membrane Glycoproteins
    116 rdf:type schema:DefinedTerm
    117 N9951d1b6c8d148eb87591817ed68bccc schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    118 schema:name Lymphokines
    119 rdf:type schema:DefinedTerm
    120 N9f40633734534291a72bcd51d627162c schema:name readcube_id
    121 schema:value cd32cd23f36ef62aab45fe984efc317217ba0d63b6df266056328f293a1a7263
    122 rdf:type schema:PropertyValue
    123 Na9f97754c9d84c2dbed850a6b6d04109 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    124 schema:name Angiopoietin-2
    125 rdf:type schema:DefinedTerm
    126 Naf42731b36cd4900b761e067250b07f3 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    127 schema:name Vascular Endothelial Growth Factor A
    128 rdf:type schema:DefinedTerm
    129 Nb0738ce4633540b89e3ed7a39caa3d65 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    130 schema:name Endothelial Growth Factors
    131 rdf:type schema:DefinedTerm
    132 Nba5a909ba53e428a8f57de8ff9bd0b5c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    133 schema:name Angiopoietin-1
    134 rdf:type schema:DefinedTerm
    135 Nbc4459251f104fdb82bea24ed064e82a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    136 schema:name Models, Biological
    137 rdf:type schema:DefinedTerm
    138 Nc2129a9eb40c4076921f4f557a0405c5 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    139 schema:name Animals
    140 rdf:type schema:DefinedTerm
    141 Nec16a6f95df741caa274a295d63e44b2 rdf:first sg:person.01233506031.30
    142 rdf:rest Nf0cacecb4c1246febe0bb16e9539edee
    143 Nf0cacecb4c1246febe0bb16e9539edee rdf:first sg:person.01274702531.47
    144 rdf:rest rdf:nil
    145 Nf358e85c420c4c68ab96e3d864c959c1 schema:name Springer Nature - SN SciGraph project
    146 rdf:type schema:Organization
    147 anzsrc-for:06 schema:inDefinedTermSet anzsrc-for:
    148 schema:name Biological Sciences
    149 rdf:type schema:DefinedTerm
    150 anzsrc-for:0601 schema:inDefinedTermSet anzsrc-for:
    151 schema:name Biochemistry and Cell Biology
    152 rdf:type schema:DefinedTerm
    153 sg:journal.1097543 schema:issn 0950-9232
    154 1476-5594
    155 schema:name Oncogene
    156 rdf:type schema:Periodical
    157 sg:person.01233506031.30 schema:affiliation https://www.grid.ac/institutes/grid.418961.3
    158 schema:familyName Wiegand
    159 schema:givenName S J
    160 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01233506031.30
    161 rdf:type schema:Person
    162 sg:person.01274702531.47 schema:affiliation https://www.grid.ac/institutes/grid.418961.3
    163 schema:familyName Yancopoulos
    164 schema:givenName G D
    165 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01274702531.47
    166 rdf:type schema:Person
    167 sg:person.0701501306.40 schema:affiliation https://www.grid.ac/institutes/grid.418961.3
    168 schema:familyName Holash
    169 schema:givenName J
    170 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0701501306.40
    171 rdf:type schema:Person
    172 sg:pub.10.1007/978-3-642-59953-8_1 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023492449
    173 https://doi.org/10.1007/978-3-642-59953-8_1
    174 rdf:type schema:CreativeWork
    175 sg:pub.10.1007/bf00334878 schema:sameAs https://app.dimensions.ai/details/publication/pub.1009431133
    176 https://doi.org/10.1007/bf00334878
    177 rdf:type schema:CreativeWork
    178 sg:pub.10.1038/362841a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1013132150
    179 https://doi.org/10.1038/362841a0
    180 rdf:type schema:CreativeWork
    181 sg:pub.10.1038/367576a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1016282476
    182 https://doi.org/10.1038/367576a0
    183 rdf:type schema:CreativeWork
    184 sg:pub.10.1038/376062a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021421211
    185 https://doi.org/10.1038/376062a0
    186 rdf:type schema:CreativeWork
    187 sg:pub.10.1038/376070a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033168641
    188 https://doi.org/10.1038/376070a0
    189 rdf:type schema:CreativeWork
    190 sg:pub.10.1038/380435a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034005847
    191 https://doi.org/10.1038/380435a0
    192 rdf:type schema:CreativeWork
    193 sg:pub.10.1038/380439a0 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004384986
    194 https://doi.org/10.1038/380439a0
    195 rdf:type schema:CreativeWork
    196 sg:pub.10.1038/nm0295-149 schema:sameAs https://app.dimensions.ai/details/publication/pub.1025343841
    197 https://doi.org/10.1038/nm0295-149
    198 rdf:type schema:CreativeWork
    199 sg:pub.10.1038/sj.onc.1201090 schema:sameAs https://app.dimensions.ai/details/publication/pub.1009788098
    200 https://doi.org/10.1038/sj.onc.1201090
    201 rdf:type schema:CreativeWork
    202 https://app.dimensions.ai/details/publication/pub.1074261048 schema:CreativeWork
    203 https://app.dimensions.ai/details/publication/pub.1082424606 schema:CreativeWork
    204 https://app.dimensions.ai/details/publication/pub.1082876818 schema:CreativeWork
    205 https://app.dimensions.ai/details/publication/pub.1083169022 schema:CreativeWork
    206 https://doi.org/10.1016/s0002-9440(10)65733-1 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012260400
    207 rdf:type schema:CreativeWork
    208 https://doi.org/10.1016/s0014-5793(99)00378-6 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034707757
    209 rdf:type schema:CreativeWork
    210 https://doi.org/10.1016/s0092-8674(00)80108-7 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042440169
    211 rdf:type schema:CreativeWork
    212 https://doi.org/10.1016/s0092-8674(00)81810-3 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023164650
    213 rdf:type schema:CreativeWork
    214 https://doi.org/10.1016/s0092-8674(00)81812-7 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020325309
    215 rdf:type schema:CreativeWork
    216 https://doi.org/10.1016/s0092-8674(00)81813-9 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012641956
    217 rdf:type schema:CreativeWork
    218 https://doi.org/10.1056/nejm197108122850711 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042994614
    219 rdf:type schema:CreativeWork
    220 https://doi.org/10.1056/nejm197111182852108 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031952402
    221 rdf:type schema:CreativeWork
    222 https://doi.org/10.1073/pnas.92.3.768 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006823065
    223 rdf:type schema:CreativeWork
    224 https://doi.org/10.1073/pnas.95.15.8795 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037720209
    225 rdf:type schema:CreativeWork
    226 https://doi.org/10.1073/pnas.95.15.8829 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003453811
    227 rdf:type schema:CreativeWork
    228 https://doi.org/10.1093/jnci/82.1.4 schema:sameAs https://app.dimensions.ai/details/publication/pub.1051237830
    229 rdf:type schema:CreativeWork
    230 https://doi.org/10.1101/gad.8.16.1897 schema:sameAs https://app.dimensions.ai/details/publication/pub.1009594234
    231 rdf:type schema:CreativeWork
    232 https://doi.org/10.1126/science.277.5322.55 schema:sameAs https://app.dimensions.ai/details/publication/pub.1062557236
    233 rdf:type schema:CreativeWork
    234 https://doi.org/10.1126/science.282.5388.468 schema:sameAs https://app.dimensions.ai/details/publication/pub.1062562857
    235 rdf:type schema:CreativeWork
    236 https://doi.org/10.1126/science.284.5422.1994 schema:sameAs https://app.dimensions.ai/details/publication/pub.1062565623
    237 rdf:type schema:CreativeWork
    238 https://doi.org/10.1161/01.res.81.4.567 schema:sameAs https://app.dimensions.ai/details/publication/pub.1063341158
    239 rdf:type schema:CreativeWork
    240 https://doi.org/10.1172/jci117857 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024866358
    241 rdf:type schema:CreativeWork
    242 https://doi.org/10.1172/jci119740 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045876259
    243 rdf:type schema:CreativeWork
    244 https://doi.org/10.1172/jci5028 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022103776
    245 rdf:type schema:CreativeWork
    246 https://doi.org/10.3171/jns.1994.81.6.0902 schema:sameAs https://app.dimensions.ai/details/publication/pub.1071097435
    247 rdf:type schema:CreativeWork
    248 https://www.grid.ac/institutes/grid.418961.3 schema:alternateName Regeneron (United States)
    249 schema:name Regeneron Pharmaceuticals, Inc., 777 Old Saw Mill River Road, Tarrytown, New York, NY 10591, USA
    250 rdf:type schema:Organization
     




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


    ...