肿瘤相关成纤维细胞在促进子宫内膜癌细胞上皮间质转化中的作用及机制研究

Recent research showed that cancer-associated fibroblasts (CAFs), the most common cellular population found in the tumor microenvironment, played an important role in the invasion and metastasis of tumor and epithelial-mesenchymal transition (EMT) was an important biological process of acquisition of invasion and metastasis ability in malignant tumor. Our preliminary study showed that the activated CAFs appeared on the edge of metastatic lymph node of endometrial cancer, and the expression of EMT markers was up-regulated in metastatic lymph node compared with primary cancer. It indicated that CAFs maybe induce EMT of endometrial cancer cells to promote invasion and metastasis. Next we will treat endometrial cancer cell lines with conditioned medium of endometrial cancer CAFs and try to study the promotion of EMT by CAFs, invasion, metastasis and stemness of cancer cells in vitro and in vivo. Moreover, we will use gene array and ELISA detection to screen different genes and cytokines about signal pathway between CAFs and normal fibroblasts (NFs), and further explore the mechanism of EMT induced by CAFs in endometrial cancer. The research was aimed to illustrate the effection of tumor microenvironment on the malignant biological behavior of endometrial cancer and serve as basis and new strategy for endometrial cancer clinical treatment.

近年研究表明肿瘤相关成纤维细胞(CAFs)作为肿瘤微环境中的主要细胞成分在肿瘤的侵袭和转移过程中发挥着重要作用，而上皮间质转化（EMT）是恶性肿瘤细胞获得迁移和侵袭能力的重要生物学过程。我们前期研究在子宫内膜癌转移淋巴结中发现EMT表达标志上调，且在其边缘发现活化的CAFs，预示CAFs可能通过诱导EMT来促进侵袭和转移。下一步我们将提取子宫内膜癌CAFs的培养上清作用于子宫内膜癌细胞株，通过体内体外实验来验证CAFs是否促进癌细胞EMT以及对侵袭转移能力和癌干细胞特性的影响，最终通过基因芯片、ELISA检测等来分析CAFs和正常成纤维细胞之间的基因表达和分泌细胞因子的差异，进一步在信号通路水平探讨CAFs促进癌细胞EMT的具体机制。本研究旨在通过阐明CAFs在促进子宫内膜癌细胞EMT中的作用，揭示肿瘤微环境对肿瘤恶性生物学行为的影响，为子宫内膜癌的临床治疗提供实验基础和新策略。