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)...

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2016 Oct 21

PMID 27756837

Citations 18

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

Affiliations

Soon will be listed here.

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.

Citing Articles

Euphorbia factor L2 suppresses the generation of liver metastatic ascites in breast cancer via inhibiting NLRP3 inflammasome activation.

Jiang D, Liu X, Tan R, Zhu Y, Zhang L Int J Mol Med. 2023; 53(1).

PMID: 38063231 PMC: 10712698. DOI: 10.3892/ijmm.2023.5332.

MicroRNAs Present in Malignant Pleural Fluid Increase the Migration of Normal Mesothelial Cells In Vitro and May Help Discriminate between Benign and Malignant Effusions.

Marques M, Pont M, Hidalgo I, Sorolla M, Parisi E, Salud A Int J Mol Sci. 2023; 24(18).

PMID: 37762343 PMC: 10531386. DOI: 10.3390/ijms241814022.

Effectiveness and safety of human type 5 recombinant adenovirus (H101) in malignant tumor with malignant pleural effusion and ascites: A multicenter, observational, real-world study.

Wang B, Zhong C, Liao Z, Wang H, Cai X, Zhang Y Thorac Cancer. 2023; 14(30):3051-3057.

PMID: 37675621 PMC: 10599969. DOI: 10.1111/1759-7714.15101.

Malignant ascites supernatant enhances the proliferation of gastric cancer cells partially via the upregulation of asparagine synthetase.

Jiao Y, Peng X, Wang Y, Hao Z, Chen L, Wu M Oncol Lett. 2023; 26(4):418.

PMID: 37664666 PMC: 10472050. DOI: 10.3892/ol.2023.14005.

Genomic and Transcriptomic Analyses of Malignant Pleural Mesothelioma (MPM) Samples Reveal Crucial Insights for Preclinical Testing.

Laure A, Rigutto A, Kirschner M, Opitz L, Grob L, Opitz I Cancers (Basel). 2023; 15(10).

PMID: 37345150 PMC: 10216513. DOI: 10.3390/cancers15102813.

References

Raulet D, Guerra N . Oncogenic stress sensed by the immune system: role of natural killer cell receptors. Nat Rev Immunol. 2009; 9(8):568-80. PMC: 3017432. DOI: 10.1038/nri2604. View

Brabletz T, Jung A, Spaderna S, Hlubek F, Kirchner T . Opinion: migrating cancer stem cells - an integrated concept of malignant tumour progression. Nat Rev Cancer. 2005; 5(9):744-9. DOI: 10.1038/nrc1694. View

Larue L, Bellacosa A . Epithelial-mesenchymal transition in development and cancer: role of phosphatidylinositol 3' kinase/AKT pathways. Oncogene. 2005; 24(50):7443-54. DOI: 10.1038/sj.onc.1209091. View

Lonardo E, Hermann P, Mueller M, Huber S, Balic A, Miranda-Lorenzo I . Nodal/Activin signaling drives self-renewal and tumorigenicity of pancreatic cancer stem cells and provides a target for combined drug therapy. Cell Stem Cell. 2011; 9(5):433-46. DOI: 10.1016/j.stem.2011.10.001. View

Ahmed N, Stenvers K . Getting to know ovarian cancer ascites: opportunities for targeted therapy-based translational research. Front Oncol. 2013; 3:256. PMC: 3782691. DOI: 10.3389/fonc.2013.00256. View

Liu S, Dontu G, Mantle I, Patel S, Ahn N, Jackson K . Hedgehog signaling and Bmi-1 regulate self-renewal of normal and malignant human mammary stem cells. Cancer Res. 2006; 66(12):6063-71. PMC: 4386278. DOI: 10.1158/0008-5472.CAN-06-0054. View

Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W . Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004; 350(23):2335-42. DOI: 10.1056/NEJMoa032691. View

Dean M, Fojo T, Bates S . Tumour stem cells and drug resistance. Nat Rev Cancer. 2005; 5(4):275-84. DOI: 10.1038/nrc1590. View

Thiery J, Acloque H, Huang R, Nieto M . Epithelial-mesenchymal transitions in development and disease. Cell. 2009; 139(5):871-90. DOI: 10.1016/j.cell.2009.11.007. View

10.

Labelle M, Begum S, Hynes R . Direct signaling between platelets and cancer cells induces an epithelial-mesenchymal-like transition and promotes metastasis. Cancer Cell. 2011; 20(5):576-90. PMC: 3487108. DOI: 10.1016/j.ccr.2011.09.009. View

11.

Chen S, Lin Y, Jao S, Chang Y, Liu C, Lin Y . Pulmonary Adenocarcinoma in Malignant Pleural Effusion Enriches Cancer Stem Cell Properties during Metastatic Cascade. PLoS One. 2013; 8(5):e54659. PMC: 3641054. DOI: 10.1371/journal.pone.0054659. View

12.

Shiota M, Zardan A, Takeuchi A, Kumano M, Beraldi E, Naito S . Clusterin mediates TGF-β-induced epithelial-mesenchymal transition and metastasis via Twist1 in prostate cancer cells. Cancer Res. 2012; 72(20):5261-72. DOI: 10.1158/0008-5472.CAN-12-0254. View

13.

Latifi A, Luwor R, Bilandzic M, Nazaretian S, Stenvers K, Pyman J . Isolation and characterization of tumor cells from the ascites of ovarian cancer patients: molecular phenotype of chemoresistant ovarian tumors. PLoS One. 2012; 7(10):e46858. PMC: 3466197. DOI: 10.1371/journal.pone.0046858. View

14.

Rafehi S, Valdes Y, Bertrand M, McGee J, Prefontaine M, Sugimoto A . TGFβ signaling regulates epithelial-mesenchymal plasticity in ovarian cancer ascites-derived spheroids. Endocr Relat Cancer. 2015; 23(3):147-59. DOI: 10.1530/ERC-15-0383. View

15.

Lee J, Chang J, Yang W, Kim S, Park S, Park J . Albumin-induced epithelial-mesenchymal transition and ER stress are regulated through a common ROS-c-Src kinase-mTOR pathway: effect of imatinib mesylate. Am J Physiol Renal Physiol. 2011; 300(5):F1214-22. DOI: 10.1152/ajprenal.00710.2010. View

16.

Kolomainen D, AHern R, Coxon F, Fisher C, King D, Blake P . Can patients with relapsed, previously untreated, stage I epithelial ovarian cancer be successfully treated with salvage therapy?. J Clin Oncol. 2003; 21(16):3113-8. DOI: 10.1200/JCO.2003.06.119. View

17.

Tan D, Agarwal R, Kaye S . Mechanisms of transcoelomic metastasis in ovarian cancer. Lancet Oncol. 2006; 7(11):925-34. DOI: 10.1016/S1470-2045(06)70939-1. View

18.

Pattabiraman D, Weinberg R . Tackling the cancer stem cells - what challenges do they pose?. Nat Rev Drug Discov. 2014; 13(7):497-512. PMC: 4234172. DOI: 10.1038/nrd4253. View

19.

Du N, Li X, Li F, Zhao H, Fan Z, Ma J . Intrapleural combination therapy with bevacizumab and cisplatin for non-small cell lung cancer‑mediated malignant pleural effusion. Oncol Rep. 2013; 29(6):2332-40. DOI: 10.3892/or.2013.2349. View

20.

Moretta L, Moretta A . Unravelling natural killer cell function: triggering and inhibitory human NK receptors. EMBO J. 2003; 23(2):255-9. PMC: 1271745. DOI: 10.1038/sj.emboj.7600019. View