XVII型胶原蛋白通过上皮间质转化在促进皮肤鳞癌侵袭和转移中的分子机制的研究

侵袭性极强的头颈部鳞癌五年生存率仅为50%。有关鳞癌侵袭、转移的研究一直是皮肤科学界关注的重点领域之一，但机制尚未明确。我们的前期研究表明位于皮肤基底膜带的XVII型胶原蛋白（COL17）可调控角质形成细胞的迁移；COL17在癌前病变中低表达，而鳞癌高表达，且与鳞癌分化负相关；细胞划痕及transwell实验发现COL17可明显促进鳞癌细胞的侵袭，并显著的观察到了EMT即上皮间质转化的发生，及E、N-钙粘蛋白表达量的转化。但COL17促进鳞癌细胞侵袭的机制尚不清楚。本项目拟以鳞癌为研究对象，从临床标本、细胞水平和动物实验三方面，验证COL17的表达与皮肤鳞癌的侵袭和转移的相关性，阐明COL17通过与整合素（integrin）的结合，和下游激酶通路的激活，促进皮肤鳞癌侵袭和转移的分子机制，探讨COL17表达在预防或抑制鳞癌侵袭转移的作用，为皮肤鳞癌的综合治疗提供新策略。

Squamous-cell carcinomas (SCCs) has been suggested to be is the second most common cancer overall among the skin cancer patients. And these SCCs are also very aggressive and invasive.Although most cutaneous squamous cell carcinoma is curable, 4% result in nodal metastasis and 1.5% in death. Squamous cell carcinoma on head and neck is associated with severe disease- and treatment-related morbidity and has a 5-year survival rate of approximately 50%, mainly due to the strong invasive capacity. Recent studies have advanced our understanding of the molecular mechanisms of the disease.In Previous Studies, we found VII collagen, an adhension molecule,prevented the motlity and invasion,closely related the SCCs.In addition, No reports demonstrated the founctions of XVII collagen(COL17),the same adhension molecule.We recently demonstrated that collagen XVII enhances keratinocyte adhesion to collagen IV, and in P38-MAPK-dependent migration and cell signaling.From these results and references, we hypothesis COL17 have the important role at the dynamically continuous processing of the SCCs molity and invasion.These provide an important experment basis,COL17 expression and the development of SCCs stage is a supplement each other influence factors. In this studies, we use the SCCs cell lines and animal models for analyzing the relationship the expression of COL17 with the molity and invasion. Further sutdies should be checked the precautionary effect of COL17 to SCCs,a high risk of developing and malignant in the patients of epidermolysis bullsosa. The anticipated results will lay a solid foundation for comprehensively clarifying the mechanism underlying promotion of Col17 on the cell invasion of squamous cell carcinoma, and will be helpful for further understanding of function of COL17 and mechanism of cell invasion regulated it, will provide new strategy and new target for the treatment of squamous cell carcinoma.