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*

  1. Yuquan Wei
  1. From the Department of Thoracic Oncology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu 610041, China
  1. ↵2 To whom correspondence should be addressed: Dept. of Thoracic Oncology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, No. 17, Section 3 of People's South Rd., Chengdu 610041, China. Tel.: 86-28-85164063; Fax: 86-28-85164060; E-mail: wangys75{at}gmail.com.

  1. ↵1 Both authors contributed equally to this work.

  2. Edited by Xiao-Fan Wang

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.

Footnotes

  • ↵* This work was supported by National Natural Science Foundation of China Grants 81272523 and 81501609, National Basic Research Program of China Grant 2010CB529900, and Chinese Postdoctoral Special Funds Grant 2016T90856. The authors declare that they have no conflicts of interest with the contents of this article.

  • ↵Graphic This article contains supplemental Figs. S1–S4 and Tables S1 and S2.

  • Received August 11, 2016.
  • Revision received October 13, 2016.
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  1. First Published on October 18, 2016 doi: 10.1074/jbc.M116.753236 The Journal of Biological Chemistry 291, 26750-26761.
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