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.

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.

• Authors: 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
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 291 Issue 52 Pg. 26750-26761 (Dec 23 2016) ISSN: 1083-351X [Electronic] United States
• PMID: 27756837 (Publication Type: Journal Article)
• Copyright: © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Chemical References

• RNA, Messenger
• Vascular Endothelial Growth Factor A
• Phosphatidylinositol 3-Kinase
• Proto-Oncogene Proteins c-akt
• TOR Serine-Threonine Kinases

Topics

• Animals
• Apoptosis
• Ascites (genetics, metabolism, pathology)
• Blotting, Western
• Cell Proliferation
• Epithelial-Mesenchymal Transition
• Female
• Flow Cytometry
• Fluorescent Antibody Technique
• Humans
• Immunoenzyme Techniques
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasms (genetics, metabolism, pathology)
• Neoplastic Stem Cells (metabolism, pathology)
• Neovascularization, Pathologic
• Phosphatidylinositol 3-Kinase (genetics, metabolism)
• Pleural Effusion, Malignant (genetics, metabolism, pathology)
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• RNA, Messenger (genetics)
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction
• TOR Serine-Threonine Kinases (genetics, metabolism)
• Tumor Cells, Cultured
• Vascular Endothelial Growth Factor A (genetics, metabolism)
• Xenograft Model Antitumor Assays