Malignant Pleural Effusion and ascites Induce Epithelial-Mesenchymal Transition and Cancer Stem-like Cell Properties via the Vascular Endothelial Growth Factor (VEGF)/Phosphatidylinositol 3-Kinase (PI3K)/Akt/Mechanistic Target of Rapamycin (mTOR) Pathway

恶性胸腔积液和腹水通过血管内皮生长因子 (VEGF)/磷脂酰肌醇 3-激酶 (PI3K)/Akt/雷帕霉素机制靶点 (mTOR) 通路诱导上皮-间质转化和癌症干细胞样特性

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作者:Tao Yin, Guoping Wang, Sisi He, Guobo Shen, Chao Su, Yan Zhang, Xiawei Wei, Tinghong Ye, Ling Li, Shengyong Yang, Dan Li, Fuchun Guo, Zeming Mo, Yang Wan, Ping Ai, Xiaojuan Zhou, Yantong Liu, Yongsheng Wang, Yuquan Wei

Abstract

Malignant pleural effusion (PE) and ascites, common clinical manifestations in advanced cancer patients, are associated with a poor prognosis. However, the biological characteristics of malignant PE and ascites are not clarified. Here we report that malignant PE and ascites can induce a frequent epithelial-mesenchymal transition program and endow tumor cells with stem cell properties with high efficiency, which promotes tumor growth, chemoresistance, and immune evasion. We determine that this epithelial-mesenchymal transition process is mainly dependent on VEGF, one initiator of the PI3K/Akt/mechanistic target of rapamycin (mTOR) pathway. From the clinical observation, we define a therapeutic option with VEGF antibody for malignant PE and ascites. Taken together, our findings clarify a novel biological characteristic of malignant PE and ascites in cancer progression and provide a promising and available strategy for cancer patients with recurrent/refractory malignant PE and ascites.

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