炎症因子SI-CLP调控STAT3-CCL2信号轴在前列腺癌去势抵抗中的作用机制研究

我国前列腺癌发病率呈逐年上升趋势且晚期患者比例较高，而去势治疗抵抗是晚期前列腺癌患者疗效不佳和死亡的主要原因。已有报道证实STAT3-CCL2信号轴活化与前列腺癌去势抵抗密切相关，去势抵抗性前列腺癌组织中CCL2表达上调，而炎症因子SI-CLP（stabilin-1 interacting chitinase-like protein）表达受抑制。我们的前期研究显示SI-CLP可抑制前列腺癌细胞去势治疗过程中STAT3磷酸化，下调CCL2分泌及其介导的单核巨噬细胞趋化。据此推测:前列腺癌细胞在去势治疗中下调SI-CLP表达，进而激活STAT3-CCL2信号通路并促进单核巨噬细胞迁入肿瘤组织，加剧去势治疗抵抗。进一步研究拟采用免疫共沉淀、氨基酸点突变等方法阐明去势治疗下调前列腺癌细胞内SI-CLP表达的具体信号通路，为从分子功能上鉴定出晚期前列腺癌患者诊治及预后评估新靶标的目标奠定理论基础。

The incidence rate of prostate cancer is increasing rapidly in China, and the proportion of advanced patients is high. Castration-resistance is the main cause for poor prognosis and increased deaths of advanced prostate cancer patients. It has been reported that the activation of STAT3-CCL2 signal axis is closely related to castration-resistance in prostate cancer. The expression of CCL2 is up-regulated in castration-resistant prostate cancer, while the expression of inflammatory factor SI-CLP is inhibited. Our previous study showed that SI-CLP could inhibit STAT3 phosphorylation, decreasing CCL2 secretion and monocytes chemotaxis in prostate cancer cells. It is speculated that prostate cancer cells survival from castration via downregulating the expression of SI-CLP, which activates STAT3-CCL2 signaling pathway and promotes the migration of monocytes into tumor tissue. Further study would use immunoprecipitation, amino acid point mutation and other methods to clarify the specific signal pathway of decreased SI-CLP expression in castration-resistant prostate cancer cells, so as to lay a theoretical foundation for identifying new targets for diagnosis, treatment and prognosis evaluation of patients with advanced prostate cancer.