Gankyrin促进TAM浸润及M2型极化在卵巢癌发展中的机制研究

It is known to us all that the infiltration and M2 polarization of tumor-associated macrophages(TAM) play a critical role in progression of epithelial ovarian cancer(EOC) . However, the mechanism of how TAMs promote tumor progression need to be fully elucidated. We have confirmed that Gankyrin facilitates EOC tumor growth and metastasis and also promotes TAM and M2 type TAM expression. Through co-culture model of ovarian cancer cell line with TAM, we also found that Gankyrin could enhance the invasiveness of TAM as well as the expression of marks of M2 type TAM. Here, we speculate that Gankyrin facilitates EOC progression through infiltration and M2 polarization of TAM. Both in vitro and in vivo models will be used in this study to clarify the effect of Gankyrin facilitating infiltration and M2 polarization of TAM. Moreover, clinical samples will also be analyzed to find the correlation and predict value of Gankyrin and TAM for clinical stage, metastasis and prognosis of ovarian cancer . We hope this study can offer better understanding of the pathogenesis for ovarian cancer progression and find a successful molecular target for treatment of ovarian cancer.

目前已知，肿瘤相关巨噬细胞（TAM）浸润及M2型极化在促进上皮性卵巢癌（EOC）发展中起重要作用，但具体机制未阐明。申请者在前期工作中发现过表达Gankyrin可以促进卵巢肿瘤生长及转移，进一步检测发现Gankyrin促进TAM及M2型TAM表达。通过建立卵巢癌细胞-TAM共培养体系，我们发现Gankyrin可促进TAM侵袭及M2型TAM特征分子表达。因此我们提出假设：Gankyrin通过促进TAM浸润及M2型极化促进卵巢癌发展。本项目拟在此基础上，在细胞和动物模型中进一步深入探讨在卵巢癌中Gankyrin促进TAM浸润及M2型极化的作用方式和调控分子机制，解析下游效应途径及靶点，同时从大样本分析总结Gankyrin及TAM对于卵巢癌临床分期、转移的相关性和预后判断价值。为完善上皮性卵巢癌发展的病因提供新的实验依据，同时也为临床靶向治疗提供新的靶点。