卵巢癌早期就易发生侵袭转移，已知肿瘤相关巨噬细胞（TAMs）和肿瘤相关成纤维细胞（TAFs）是基质微环境中与肿瘤侵袭转移密切相关的两大类基质细胞，我们前期发现卵巢癌细胞外分泌蛋白CTHRC1主要分布于转移灶基质中，其周围富集M2型TAMs分布及TAFs分泌的免疫因子，提示外泌蛋白CTHRC1作为卵巢癌细胞与基质细胞间的“媒介桥梁”促进肿瘤转移。本课题将进一步从癌细胞与基质细胞之间免疫调控的角度，以卵巢癌细胞、TAFs、TAMs、免疫系统人源化SCID小鼠、卵巢癌患者为研究对象，体内、外实验系统探讨以CTHRC1介导的PI3K/Akt及JAK/STAT信号通路在肿瘤基质免疫重塑（免疫活性因子、TAMs-M1/M2分型及CD3+CD8+T细胞激活）与卵巢癌侵袭转移的关系及相关机制，为寻找新型免疫治疗的靶点分子及卵巢癌诊断与治疗的靶标提供理论基础。

Ovarian cancer is more likely to metastasis at a very early stage, but the mechanism is still not clear. As well known, TAMs and TAFs are two important stromal cells in the stromal microenvironment which related to tumor invasion and metastasis. Previously, we discovered collagen triple helix repeat containing-1 (CTHRC1) expression was up-regulated in the stroma of epithelial ovarian cancer (EOC) tissues, surrounding by enriched M2 type-tumor associated macrophage (TAMs) and immune factors secreted by tumor associated fibroblasts (TAFs). In this study, we intend to fully investigate the biological characteristics of CTHRC1 in vitro and in vivo using ovarian cancer cell lines, TAMs, TAFs, SCID mouse and EOC patients as models, and obtain evidence of direct causal relationship between the immune regulation in tumor stroma microenvironment and the metastasis of EOC. Further steps are designed to clarify the mechanism that CTHRC1 mediated PI3K/Akt and JAK/STAT signaling pathway in the tumor immune matrix remodeling, including immune active factors releasing, TAMs-M1/M2 type and CD3+ CD8+ T cell activation and its relationship with metastasis of EOC. A complete comprehensive knowledge of characteristics of CTHRC1 in EOC would help better understand the pathogenesis of EOC and resolve practical problems regarding to diagnosis, treatment, and follow-up, thus provide great values in clinical application, especially in immune therapy.