卵巢癌干细胞促进卵巢癌细胞侵袭转移的作用及机制研究

Cancer metastasis is the most important obstacle to cure ovarian cancer in clinic, cancer stem cells(CSCs) are the source of tumor recurrence and metastasis. Our previous studies showed that Ovarian CSCs(OCSCs)induced ovarian cancer cell epithelial-mesenchymal transition (EMT),then let ovarian cancer cell get more invasive and metastatic ability. OCSCs secreted large amounts of chemokines and ovarian cancer cells expressiong the corresponding chemokine receptor. We speculated: OCSCs by secreting the chemokins(eg,CCL5,CXCL16,CXCL10,CXCL1,etc.)to promote ovarian cancer cell EMT,and thus facilitate the invasion and metastasis of ovarian cancer cells.In this project based, antibodies blocking and specific shRNA silencing were used to clarify the critical chemokines/receptors shaft that mediated the effect of OCSCs promote ovarian cancer cells invasion and metastasis. Western blot,immunofluorescence and other technology were used to explore the underlying mechanisms of chemokines/receptors shaft that mediated the effect of OCSCs promote ovarian cancer cells EMT and metastasis.Clinical sample to further verify the above phenomenon and mechanisms,and its relationship with clinical outcome. The project will not only elucidate the specific melecular mechanism of metastasis and recurrence of ovarian cancer,but also provides new idea for the prevention and treatment of metastasis in ovarian cancer.

侵袭转移是临床卵巢癌治疗的最大障碍；肿瘤干细胞则是肿瘤复发转移的根源。申请者基于前期研究发现：卵巢癌干细胞（OCSCs）可使卵巢癌细胞发生上皮间充质转化（EMT），进而获得更强的侵袭和转移能力；OCSCs分泌大量的趋化因子，且卵巢癌细胞表达相应的趋化因子受体，我们推测：OCSCs可通过分泌趋化因子（如CCL5，CXCL16，CXCL10，CXCL1等）促进卵巢癌细胞EMT，继而促进卵巢癌细胞侵袭和转移。本项目拟在前期工作的基础上，采用抗体阻断及特异性shRNA，体外及荷瘤小鼠模型明确OCSCs促进卵巢癌细胞侵袭转移的关键趋化因子/受体轴；采用Western blot、免疫荧光等方法探讨OCSCs通过分泌特定的趋化因子促进卵巢癌细胞上皮间充质转化的相关信号通路；通过临床标本相关性分析验证上述现象和机制。通过本项目，不但能完善卵巢癌转移和复发的分子机制，而且也将为临床侵袭转移的防治提供新思路。

侵袭转移是临床卵巢癌治疗的最大障碍；肿瘤干细胞则是肿瘤复发转移的根源。申请者根据前期发现卵巢癌干细胞（ OCSCs）可使卵巢癌细胞发生上皮间充质转化.（ EMT），进而获得更强的侵袭和转移能力； OCSCs 分泌大量的趋化因子，且卵巢癌细胞表达相应的趋化因子受体，因此推测： OCSCs 可通过分泌趋化因子促进卵巢癌细胞 EMT，继而促进卵巢癌细胞侵袭和转移。本项目在前期工作的基础上，采用抗体阻断及特异性 shRNA，体外及荷瘤小鼠模型明确 了CCL5是OCSCs 促进卵巢癌细胞侵袭转移的关键趋化因子/受体轴；采用 Western blot、免疫荧光等方法探讨 OCSCs 通过分泌CCL5促进卵巢癌细胞上皮间充质转化的NFKB相关信号通路；通过临床标本相关性分析验证上述现象和机制。通过本项目，不但能完善卵巢癌转移和复发的分子机制，而且也将为临床侵袭转移的防治提供新思路。在项目资助期间发表SCI论文2篇，每篇均IF>5，其中带基金标注2篇。