CAFs来源的Asporin通过CD44受体调控TGF-β信号通路参与卵巢癌化疗耐药的作用及机制

卵巢癌恶性程度高、预后差，化疗耐药是临床上亟需解决的问题。肿瘤相关性纤维母细胞（CAFs）促进了卵巢癌化疗耐药，然而机制尚未阐明。Asporin是一种细胞外基质蛋白，其能促进多种肿瘤的进展。我们前期发现，Asporin在卵巢癌间质的CAFs中高表达，且和化疗耐药高度相关，已有研究表明TGF-β信号通路在调控卵巢癌化疗耐药中发挥着重要作用，同时我们还发现，CAFs来源的Asporin可促进卵巢癌SKOV3细胞中TGF-β1的表达，因此我们推测，CAFs来源的Asporin通过TGF-β信号通路发挥了促进卵巢癌化疗耐药的作用。本项目拟通过临床标本验证Asporin在卵巢癌中的表达定位及临床意义；细胞和动物实验探究CAFs来源的Asporin 通过TGF-β通路促进卵巢癌化疗耐药的作用及机制。该研究有助于阐明CAFs在卵巢癌化疗耐药中的具体机制，从卵巢癌微环境的角度为卵巢癌的治疗提供新的思路。

Ovarian cancer has a high degree of malignancy and a poor prognosis. Chemotherapy resistance is a clinically urgent problem to be solved. Cancer-associated-fibroblasts(CAFs) promote chemotherapy resistance of ovarian cancer, however the mechanism has not yet been elucidated. Asporin is an extracellular matrix protein that can promote the progression of various tumors. We have previously found that Asporin is highly expressed in CAFs in the stromal ovarian cancer and is highly correlated with chemotherapy resistance. Studies have shown that TGF-β signaling pathway plays an important role in regulating chemotherapy resistance of ovarian cancer. At the same time, we also found that Asporin derived from CAFs can promote the expression of TGF-β1 in ovarian cancer SKOV3 cells. Therefore, we speculate that Asporin derived from CAFs plays a role in promoting chemotherapy resistance of ovarian cancer through the TGF-β signaling pathway. This project intends to verify the expression, location and clinical significance of Asporin in ovarian cancer through clinical specimens and to explore the role and mechanism of CAFs-derived Asporin in promoting ovarian cancer chemotherapy resistance through the TGF-β pathway by cell and animal experiments. This study helps to clarify the specific mechanism of CAFs in ovarian cancer chemotherapy resistance, and provides new ideas for the treatment of ovarian cancer from the perspective of ovarian cancer microenvironment.