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Am J Pathol. 2016 Apr;186(4):1055-64. doi: 10.1016/j.ajpath.2015.11.021. Epub 2016 Feb 11.

Neuropilin 1 Receptor Is Up-Regulated in Dysplastic Epithelium and Oral Squamous Cell Carcinoma.

Author information

1
Vascular Biology Program, Boston Children's Hospital, Boston, Massachusetts.
2
Department of Stomatology, Dental School of the University of Sao Paulo, Brazil.
3
Center for Vascular Biology Research, Beth Israel Deaconess Hospital, Boston, Massachusetts.
4
Vascular Biology Program, Boston Children's Hospital, Boston, Massachusetts; Department of Surgery, Harvard Medical School, Boston, Massachusetts.
5
Vascular Biology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
6
Center for Vascular Biology Research, Beth Israel Deaconess Hospital, Boston, Massachusetts; Department of Pathology, Harvard Medical School, Boston, Massachusetts.
7
Department of Opthalmology, Harvard Medical School, Boston, Massachusetts; Massachusetts Eye and Ear Infirmary, Boston, Massachusetts.
8
Vascular Biology Program, Boston Children's Hospital, Boston, Massachusetts; Department of Surgery, Harvard Medical School, Boston, Massachusetts. Electronic address: diane.bielenberg@childrens.harvard.edu.

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.

PMID:
26877262
PMCID:
PMC4822338
DOI:
10.1016/j.ajpath.2015.11.021
[Indexed for MEDLINE]
Free PMC Article

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