title: Neuropilin 1 expression correlates with differentiation status of epidermal cells and cutaneous squamous cell carcinomas.
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.
authors.affiliation: Vascular Biology Program, Department of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Shokoufeh
authors.initials: S
authors.lastname: Shahrabi-Farahani
authors.affiliation: Vascular Biology Program, Department of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.affiliation: Vascular Biology Program, Department of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Bernadette M M
authors.initials: BM
authors.lastname: Zwaans
authors.affiliation: Vascular Biology Program, Department of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Jeans M
authors.initials: JM
authors.lastname: Santana
authors.affiliation: Vascular Biology Program, Department of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Akio
authors.initials: A
authors.lastname: Shimizu
authors.affiliation: Vascular Biology Program, Department of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Seiji
authors.initials: S
authors.lastname: Takashima
authors.affiliation: Vascular Biology Program, Department of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Kreuter
authors.affiliation: Vascular Biology Program, Department of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Leigh
authors.initials: L
authors.lastname: Coultas
authors.affiliation: Vascular Biology Program, Department of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: D'Amore
authors.affiliation: Vascular Biology Program, Department of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Arbeit
authors.affiliation: Vascular Biology Program, Department of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Lars A
authors.initials: LA
authors.lastname: Akslen
authors.affiliation: Vascular Biology Program, Department of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Diane R
authors.initials: DR
authors.lastname: Bielenberg
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D053556:Keratin-1 / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008822:Mice, Transgenic; D039942:Neuropilin-1 / Q000235:genetics / Q000378:metabolism*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014183:Transplantation, Heterologous; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D053556:Keratin-1; D042461:Vascular Endothelial Growth Factor A; D039942:Neuropilin-1; D040262:Receptors, Vascular Endothelial Growth Factor