膀胱癌微囊泡在诱导EPC向肿瘤相关成纤维细胞分化中的作用及其机制

Tumor-associated fibroblast (TAF), as an important messenger of cross-talk between bladder cancer cells and tumor microenvironment, plays an important role in the progression of bladder cancer. Studies have shown that cancer cell-derived microvesicles can induce the formation of TAF, but the specific mechanism is unclear. Our previous studies found that: 1. bladder cancer cell-derived microvesicles can be swallowed by endothelial progenitor cell (EPC) to promote the differentiation of EPC into TAF; 2, TAF can enhance the angiogenic characteristics of endothelial cells; 3, CB-839 can inhibit the activity of glutaminase, and then inhibit the secretion of microvesicles. We speculated that bladder cancer cell-derived microvesicles can induce EPC to differentiate into TAF and promote angiogenesis of bladder cancer, and CB-839 can inhibit the secretion of microvesicles by bladder cancer cells, which provides a new idea for the treatment of bladder cancer patients. The purpose of this project is to study the biological effect and mechanism of bladder cancer cell-derived microvesicles on EPC in vivo and in vitro, and to explore the transformation of EPC to TAF and its effect on angiogenesis, which can provide an important theoretical basis for the treatment of bladder cancer.

肿瘤相关成纤维细胞（TAF）作为膀胱癌细胞与肿瘤微环境产生交互对话的重要信使，在膀胱癌的进展中具有重要作用。研究表明肿瘤细胞微囊泡可诱导TAF形成，但具体机制尚不明确。我们前期研究发现：1、膀胱癌微囊泡可以被内皮祖细胞（EPC）内吞，促进EPC向TAF分化；2、TAF可增强内皮细胞成血管特征；3、CB-839可通过抑制谷氨酰胺酶的活性，进而抑制微囊泡的分泌。我们推测：膀胱癌微囊泡可诱导EPC向TAF分化，促进膀胱癌的血管形成；CB-839可抑制膀胱癌微囊泡的分泌，为膀胱癌患者的治疗提供新思路。本项目拟开展体内、体外研究，观察膀胱癌微囊泡对EPC的生物学作用及机制；探讨EPC向TAF转化对血管生成特征的影响，可为膀胱癌的治疗提供重要的理论依据。

肿瘤相关成纤维细胞（TAF）作为癌细胞与肿瘤微环境产生交互对话的信使，在膀胱癌的进展中具有重要作用。研究表明肿瘤细胞微囊泡可诱导TAF形成，但具体机制尚不明确。我们前期预实验发现：1、膀胱癌微囊泡可以被EPC内吞，促进EPC向TAF分化；2、TAF细胞上清可增强内皮细胞成血管特征；3、CB-839可抑制谷氨酰胺酶，减少微囊泡的分泌。我们提出科学假说：膀胱癌微囊泡可诱导EPC向TAF分化，促进膀胱癌的血管形成；CB-839可抑制膀胱癌微囊泡分泌，为膀胱癌患者的治疗提供新思路。本项目在体内、体外水平探讨了膀胱癌微囊泡对EPC的生物学作用及机制；探讨EPC向TAF转化以及对血管生成特征的影响；以抑制膀胱癌微囊泡为策略，论证通过应用了CB-839抑制TAF的形成治疗膀胱癌的可行性。目前未见相关研究报道，本研究有望为膀胱癌患者的临床治疗提供新希望。