Neuropilin 1 expression correlates with differentiation status of epidermal cells and cutaneous squamous cell carcinomas View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-05-05

AUTHORS

Shokoufeh Shahrabi-Farahani, Lili Wang, Bernadette MM Zwaans, Jeans M Santana, Akio Shimizu, Seiji Takashima, Michael Kreuter, Leigh Coultas, Patricia A D'Amore, Jeffrey M Arbeit, Lars A Akslen, Diane R Bielenberg

ABSTRACT

Neuropilins (NRPs) are cell surface receptors for vascular endothelial growth factor (VEGF) and SEMA3 (class 3 semaphorin) family members. The role of NRPs in neurons and endothelial cells has been investigated, but the expression and role of NRPs in epithelial cells is much less clear. Herein, the expression and localization of NRP1 was investigated in human and mouse skin and squamous cell carcinomas (SCCs). Results indicated that NRP1 mRNA and protein was expressed in the suprabasal epithelial layers of the skin sections. NRP1 staining did not overlap with that of keratin 14 (K14) or proliferating cell nuclear antigen, but did co-localize with staining for keratin 1, indicating that differentiated keratinocytes express NRP1. Similar to the expression of NRP1, VEGF-A was expressed in suprabasal epithelial cells, whereas Nrp2 and VEGFR2 were not detectable in the epidermis. The expression of NRP1 correlated with a high degree of differentiation in human SCC specimens, human SCC xenografts, and mouse K14-HPV16 transgenic SCC. UVB irradiation of mouse skin induced Nrp1 upregulation. In vitro, Nrp1 was upregulated in primary keratinocytes in response to differentiating media or epidermal growth factor-family growth factors. In conclusion, the expression of NRP1 is regulated in the skin and is selectively produced in differentiated epithelial cells. NRP1 may function as a reservoir to sequester VEGF ligand within the epithelial compartment, thereby modulating its bioactivity. More... »

PAGES

752-765

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/labinvest.2014.66

DOI

http://dx.doi.org/10.1038/labinvest.2014.66

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1003589806

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/24791743


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35 schema:description Neuropilins (NRPs) are cell surface receptors for vascular endothelial growth factor (VEGF) and SEMA3 (class 3 semaphorin) family members. The role of NRPs in neurons and endothelial cells has been investigated, but the expression and role of NRPs in epithelial cells is much less clear. Herein, the expression and localization of NRP1 was investigated in human and mouse skin and squamous cell carcinomas (SCCs). Results indicated that NRP1 mRNA and protein was expressed in the suprabasal epithelial layers of the skin sections. NRP1 staining did not overlap with that of keratin 14 (K14) or proliferating cell nuclear antigen, but did co-localize with staining for keratin 1, indicating that differentiated keratinocytes express NRP1. Similar to the expression of NRP1, VEGF-A was expressed in suprabasal epithelial cells, whereas Nrp2 and VEGFR2 were not detectable in the epidermis. The expression of NRP1 correlated with a high degree of differentiation in human SCC specimens, human SCC xenografts, and mouse K14-HPV16 transgenic SCC. UVB irradiation of mouse skin induced Nrp1 upregulation. In vitro, Nrp1 was upregulated in primary keratinocytes in response to differentiating media or epidermal growth factor-family growth factors. In conclusion, the expression of NRP1 is regulated in the skin and is selectively produced in differentiated epithelial cells. NRP1 may function as a reservoir to sequester VEGF ligand within the epithelial compartment, thereby modulating its bioactivity.
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46 SCC specimens
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51 antigen
52 bioactivity
53 carcinoma
54 cell carcinoma
55 cell nuclear antigen
56 cell surface receptors
57 cells
58 compartments
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61 cutaneous squamous cell carcinoma
62 degree
63 differentiated epithelial cells
64 differentiated keratinocytes
65 differentiation
66 differentiation status
67 endothelial cells
68 endothelial growth factor
69 epidermal cells
70 epidermal growth factor (EGF) family growth factors
71 epidermis
72 epithelial cells
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75 expression
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78 factors
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87 keratinocytes
88 layer
89 ligands
90 localization
91 mRNA
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94 mouse skin
95 neurons
96 neuropilins
97 nuclear antigen
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99 protein
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