title: 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.affiliation: 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.
authors.forename: Tao
authors.initials: T
authors.lastname: Yin
authors.affiliation: 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.
authors.forename: Guoping
authors.initials: G
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Sisi
authors.initials: S
authors.lastname: He
authors.affiliation: 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.
authors.forename: Guobo
authors.initials: G
authors.lastname: Shen
authors.affiliation: 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.
authors.forename: Chao
authors.initials: C
authors.lastname: Su
authors.affiliation: 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.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Xiawei
authors.initials: X
authors.lastname: Wei
authors.affiliation: 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.
authors.forename: Tinghong
authors.initials: T
authors.lastname: Ye
authors.affiliation: 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.
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Shengyong
authors.initials: S
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Fuchun
authors.initials: F
authors.lastname: Guo
authors.affiliation: 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.
authors.forename: Zeming
authors.initials: Z
authors.lastname: Mo
authors.affiliation: 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.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wan
authors.affiliation: 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.
authors.forename: Ping
authors.initials: P
authors.lastname: Ai
authors.affiliation: 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.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Zhou
authors.affiliation: 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.
authors.forename: Yantong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: 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 wangys75@gmail.com.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
mesh_terms: D000818:Animals; D017209:Apoptosis; D001201:Ascites / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015153:Blotting, Western; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D009389:Neovascularization, Pathologic; D058539:Phosphatidylinositol 3-Kinase / Q000235:genetics / Q000378:metabolism; D016066:Pleural Effusion, Malignant / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases
keywords: VEGF; ascites; cancer biology; cancer stem cells; epithelial-mesenchymal transition (EMT); malignant pleural effusion; tumor therapy