title: Neuropilin 1 Receptor Is Up-Regulated in Dysplastic Epithelium and Oral Squamous Cell Carcinoma.
abstract: Neuropilins are receptors for disparate ligands, including proangiogenic factors such as vascular endothelial growth factor and inhibitory class 3 semaphorin (SEMA3) family members. Differentiated cells in skin epithelium and cutaneous squamous cell carcinoma highly express the neuropilin-1 (NRP1) receptor. We examined the expression of NRP1 in human and mouse oral mucosa. NRP1 was significantly up-regulated in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC). NRP1 receptor localized to the outer suprabasal epithelial layers in normal tongue, an expression pattern similar to the normal skin epidermis. However, dysplastic tongue epithelium and OSCC up-regulated NRP1 in basal and proliferating epithelial layers, a profile unseen in cutaneous squamous cell carcinoma. NRP1 up-regulation is observed in a mouse carcinogen-induced OSCC model and in human tongue OSCC biopsies. Human OSCC cell lines express NRP1 protein in vitro and in mouse tongue xenografts. Sites of capillary infiltration into orthotopic OSCC tumors correlate with high NRP1 expression. HSC3 xenografts, which express the highest NRP1 levels of the cell lines examined, showed massive intratumoral lymphangiogenesis. SEMA3A inhibited OSCC cell migration, suggesting that the NRP1 receptor was bioactive in OSCC. In conclusion, NRP1 is regulated in the oral epithelium and is selectively up-regulated during epithelial dysplasia. NRP1 may function as a reservoir to sequester proangiogenic ligands within the neoplastic compartment, thereby recruiting neovessels toward tumor cells.
authors.affiliation: Vascular Biology Program, Boston Children's Hospital, Boston, Massachusetts.
authors.forename: Shokoufeh
authors.initials: S
authors.lastname: Shahrabi-Farahani
authors.affiliation: Department of Stomatology, Dental School of the University of Sao Paulo, Brazil.
authors.forename: Marina
authors.initials: M
authors.lastname: Gallottini
authors.affiliation: Department of Stomatology, Dental School of the University of Sao Paulo, Brazil.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Martins
authors.affiliation: Vascular Biology Program, Boston Children's Hospital, Boston, Massachusetts.
authors.forename: Erik
authors.initials: E
authors.lastname: Li
authors.affiliation: Center for Vascular Biology Research, Beth Israel Deaconess Hospital, Boston, Massachusetts.
authors.forename: Dayna R
authors.initials: DR
authors.lastname: Mudge
authors.affiliation: Vascular Biology Program, Boston Children's Hospital, Boston, Massachusetts; Department of Surgery, Harvard Medical School, Boston, Massachusetts.
authors.forename: Hironao
authors.initials: H
authors.lastname: Nakayama
authors.affiliation: Vascular Biology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Hida
authors.affiliation: Center for Vascular Biology Research, Beth Israel Deaconess Hospital, Boston, Massachusetts; Department of Pathology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Dipak
authors.initials: D
authors.lastname: Panigrahy
authors.affiliation: Department of Opthalmology, Harvard Medical School, Boston, Massachusetts; Massachusetts Eye and Ear Infirmary, Boston, Massachusetts.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: D'Amore
authors.affiliation: Vascular Biology Program, Boston Children's Hospital, Boston, Massachusetts; Department of Surgery, Harvard Medical School, Boston, Massachusetts. Electronic address: diane.bielenberg@childrens.harvard.edu.
authors.forename: Diane R
authors.initials: DR
authors.lastname: Bielenberg
mesh_terms: D002278:Carcinoma in Situ / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D004848:Epithelium / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D012878:Skin Neoplasms / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D018040:Receptors, Neurokinin-1