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.

Immunohistochemical study on neuropilin 1 (NRP1) immunoexpression in oral squamous cell carcinoma

“…Many studies documented that the increased expression of NRP1 in the tumor cells is a poor prognostic factor in malignant neoplasm since the expression of NRP1 was correlated with advanced tumor stage and/or progression in many cancers [17,[21][22][23][24]. Our study on oral squamous cell cancer patients with or without metastases supports previous findings.…”

Neuropilin‐1 regulated by miR‐320 contributes to the growth and metastasis of cholangiocarcinoma cells

“…NRP‐1 has been shown to act as multiple co‐receptors to stimulate the proliferation of various types of cancer cells . NRP‐1 depletion inhibited the proliferation of CCA cells by inducing cell cycle arrest in the G0/G1 phase through upregulating p27 and downregulating cyclin E and CDK2.…”

“…34 NRP-1 has been shown to act as multiple co-receptors to stimulate the proliferation of various types of cancer cells. [8][9][10][11][12] NRP-1 depletion inhibited the proliferation of CCA cells by inducing cell cycle arrest in the G0/G1 phase through upregulating p27 and downregulating cyclin E and CDK2. P27 negatively regulates the cell cycle progression from G 1 to S phase by binding to and inhibiting the activity of CDKs.…”

“…The VEGF/VEGFR2 signalling pathway is critical for the growth of CCA . NRP‐1 is found to be overexpressed in and negatively correlates with the prognosis of hepatocellular carcinoma, colorectal cancer, pancreas cancer and oesophagus squamous cell carcinoma . We have recently reported that NRP‐1 is associated with clinicopathology and contributes to cell proliferation and migration in gastric cancer .…”

Lymphatic changes in cancer and drug delivery to the lymphatics in solid tumors

“…COX-2 [47,48] WNT5B [49] WNT-1 inducible signaling pathway protein-1 [50] Prox-1 [51] FOXC2 [51] VEGF-D [52] Neuropilin 1 receptor [53] IL-6 [54] VEGF-C [47,[54][55][56] Periostin [55] ID-1 [57] A C C E P T E D M A N U S C R I P T Α-smooth muscle actin protein [58] NF-κB [56] Notch1 [56] Cancer-associated fibroblasts [ Table 1. A list of the markers discussed in section 2.2.…”