Neuropilin 1 expression correlates with differentiation status of epidermal cells and cutaneous squamous cell carcinomas.

Neuropilin 1 expression correlates with differentiation status of epidermal cells and cutaneous squamous cell carcinomas.
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DOI:
10.1038/labinvest.2014.66
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发表时间:
2014-07
期刊:
Laboratory investigation; a journal of technical methods and pathology
影响因子:
--
通讯作者:
--
中科院分区:
其他
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神经毡蛋白 (NRP) 是 VEGF 和 SEMA3 家族成员的细胞表面受体。 NRP 在神经元和内皮细胞中的作用已被研究,但 NRP 在上皮细胞中的表达和作用还不太清楚。在此,研究了神经毡蛋白 1 (NRP1) 在人和小鼠皮肤和鳞状细胞癌 (SCC) 中的表达和定位。结果表明,NRP1 mRNA和蛋白在皮肤切片的基底上皮层中表达。 NRP1 染色与角蛋白 14 (K14) 或增殖细胞核抗原的染色不重叠,但与角蛋白 1 的染色共定位,表明分化的角质形成细胞表达 NRP1。与NRP1的表达相似,VEGF-A在基底上皮细胞中表达,而Nrp2和VEGFR2在表皮中未检测到。 NRP1 的表达与人 SCC 标本、人 SCC 异种移植物和小鼠 K14-HPV16 转基因 SCC 的高度分化相关。小鼠皮肤的 UVB 照射诱导 Nrp1 上调。在体外,原代角质形成细胞中的 Nrp1 在分化培养基或 EGF 家族生长因子的作用下上调。总之,NRP1 的表达在皮肤中受到调节,并在分化的上皮细胞中选择性产生。 NRP1 可能充当储库,将 VEGF 配体隔离在上皮室内,从而调节其生物活性。
Neuropilins (NRP) are cell surface receptors for VEGF and SEMA3 family members. The role of NRP in neurons and endothelial cells has been investigated, but the expression and role of NRP in epithelial cells is much less clear. Herein, the expression and localization of neuropilin 1 (NRP1) was investigated in human and mouse skin and squamous cell carcinomas (SCC). Results indicated that NRP1 mRNA and protein was expressed in the suprabasal epithelial layers of skin sections. NRP1 staining did not overlap with that of keratin 14 (K14) or proliferating cell nuclear antigen, but did colocalize 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 EGF-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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