放化疗后肿瘤微环境中外泌因子NPPC通过cGMP-MAPK信号通路促进前列腺癌恶性表型的机制研究

Prostate cancer is the most common male malignant tumor in China. Tumor microenvironment is strongly associated with cancer development and progression, however the mechanism is still unclear. Our previous data found that NPPC expression was upregulated in stromal cells after chemoradiotherapy, and it can promote the proliferation, migration and invasion of prostate cancer cells, activate cGMP-MAPK signaling pathway in vitro, and accelerate the growth of mouse xenograft tumor in vivo. It may remind us that as an important part of tumor microenvironment NPPC will promote the malignant phenotype of prostate cancer through cGMP-MAPK signaling pathway. In order to confirm this hypothesis, this subject is divided into three steps. Firstly, clinical samples before and after chemoradiotherapy are used to analyze its relevance with prostate cancer malignant degree, metastasis, survival rate in vivo. Secondly, to explore the influence of NPPC on malignant phenotype of prostate cancer, we will conduct cell experiments and xenograft tumor experiments. Thirdly, the molecular mechanism of how NPPC influence malignant phenotype of prostate cancer will be determined by cell signaling inhibitors, RNA interference and RNA-seq. The completion of this project will preliminarily clarify the mechanism of NPPC in the malignant phenotype of prostate cancer, and provide new clues and targets for prostate cancer treatment.

前列腺癌是我国男性恶性肿瘤中发病率第六位的疾病，肿瘤微环境与癌症发生发展紧密相关，但是微环境影响癌症的具体机制仍不明确。我们前期研究发现外泌因子NPPC在放化疗后的基质细胞中表达升高，在体外能促进前列腺癌细胞的增殖、迁移和侵袭，并且能激活cGMP-MAPK信号通路，在体内促进小鼠移植瘤的生长。上述研究提示NPPC作为肿瘤微环境中的重要组成成分可能通过激活cGMP-MAPK信号通路促进前列腺癌细胞的恶性表型。为证实此假设，本课题拟：1）利用放化疗前后的临床样本，分析体内条件下NPPC与前列腺癌恶性程度、转移、预后生存率等的相关性；2）通过细胞实验和小鼠移植瘤实验等探索NPPC对前列腺癌恶性表型的具体影响；3）利用抑制剂、RNA干扰和RNA-seq等方法确定NPPC促进前列腺癌恶性表型的分子机制。本项目的完成将初步阐明NPPC在前列腺癌恶性表型中的作用机制，为其治疗提供新的线索和靶标。

1前列腺癌是我国男性恶性肿瘤中发病率第六位的疾病，肿瘤微环境与癌症发生发展紧密相关，但是微环境影响癌症的具体机制仍不明确。我们研究发现外泌因子NPPC在放化疗后的基质细胞中表达升高，在体外能促进前列腺癌细胞的增殖、迁移和侵袭，并且能激活MAPK信号通路，在体内促进小鼠移植瘤的生长。上述研究提示NPPC作为肿瘤微环境中的重要组成成分可能通过激活MAPK信号通路促进前列腺癌细胞的恶性表型。本项目的完成初步阐明NPPC在前列腺癌恶性表型中的作用机制，为其治疗前列腺癌提供新的线索和靶标。