S100P上调AGTR1实现自我激活从而促进绒毛膜癌的生长和转移

绒毛膜癌是常见的妊娠相关肿瘤，具有极易发生转移的特点。本课题组一直致力于S100P在妇科肿瘤的研究。通过cDNA芯片，我们发现S100P上调细胞周期和移动相关的基因（包括AGTR1）表达，提示S100P可能与肿瘤的生长和转移有关。免疫组化发现，S100P在正常绒毛组织中只表达于合体滋养细胞，而在绒毛膜癌中却同时表达于合体滋养细胞和细胞滋养细胞。过表达S100P可促进绒癌细胞增殖与迁移，上调ERK和P38磷酸化水平，激活MAPK通路；此外S100P上调AGTR1 mRNA和蛋白的表达；据报道，S100P是钙结合蛋白，而AGTR1具有激活钙离子释放的功能；同时我们发现，对过表达S100P细胞施用AGTR1拮抗剂可导致S100P促迁移能力被逆转，提示S100P可能通过AGTR1调控细胞的迁移。本课题拟研究，S100P是否通过调控AGTR1的表达实现自我激活从而促进绒毛膜癌的生长和转移。

Choriocarcinoma is a common pregnancy associated tumor, characterized by its easily metastasis. We have been committed to investigating S100P function in infertility and gynaecological cancers since. By cDNA chip, we found S100P raised the expression level of cell-cycle and cell-motility related genes, indicated S100P might promote tumor cell growth and motility. Immunohistochemistry results showed that, S100P was only expressed in syncytiotrophoblast not cytotrophoblast in normal placental villi, comparing to its expression both in syncytiotrophoblast and cytotrophoblast of choriocarcinoma tissues. Overexpression of S100P in choriocarcinoma cells can promote proliferation and migration by the activation of MAPK pathway, enhancing ERK and P38 phosphorylation. Besides, S100P upregulated AGTR1 expression both in mRNA and protein level. S100P is a calcium ion binding protein. And AGTR1 is well known for its capability of calcium ion releasing activity. Furthermore, blocking the AGTR1 signal by its antagonist in S100P overexpression cells reversed the invasion increment by S100P. Those results suggested that AGTR1 may be involved in S100P signal activation, and S100P and AGTR1 were likely to form a positive-feedback regulation loop in choriocarcinoma cells. In this study, we will investigate whether S100P promotes the growth and motility of choriocarcinoma by self-activating through upregulating the expression of AGTR1.