The Influence of Hypoxia Microenvironment on Metastasis Induced by Epithelial-Mesenchymal Transition of Human Lung Adenocarcinoma_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

XieZhefan , DongHangming , WeiYilan , HuangChaowen ,  CaiShaoxi

Department of Respiratory Medicine, Chronic Airways Diseases Laboratory, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China;

Corresponding author：

CaiShaoxi, Email: caishaox@fimu.com

Keywords：

Lung cancer; Hypoxic; Epithelial-mesenchymal transition; Migration; Invasion

DOI：

10.7507/1671-6205.2016109

Video：

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Objective To investigate the influence of hypoxia on pro-metastasis induced by epithelial-mesenchymal transition (EMT) of human lung adenocarcinoma. Methods The human lung cancer cell line H460 was cultured in hypoxic condition and the morphologic changes of the cells were observed under the microscope. The EMT-related markers including E-cadherin and vimentin were detected by Western blot. Transwell migration assay and transwell invasion assay were employed to detect the migratory and invasive activity of cancer cells. Results Hypoxic induced morphological changes were consistent with the mesenchymal phenotype, such as an elongated fibroblastic morphology, and conversion from a tightly packed epithelial cobblestone pattern to a loosely packed scattered phenotype. Compared with the control group, hypoxic attenuated the quantity of E-cadhenrin, but increased vimentin, which resulted in promotion of migration and invasion of H460. Conclusion Hypoxia induces EMT in H460 and enhances the invasive and migratory abilities of lung cancer cells.

Citation： Xie Zhefan, Dong Hangming, Wei Yilan, Huang Chaowen, Cai Shaoxi. The Influence of Hypoxia Microenvironment on Metastasis Induced by Epithelial-Mesenchymal Transition of Human Lung Adenocarcinoma. Chinese Journal of Respiratory and Critical Care Medicine, 2016, 15(5): 465-469. doi: 10.7507/1671-6205.2016109 Copy

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13.	方美玉.进展期非小细胞肺癌药物治疗进展.中国呼吸与危重监护杂志, 2008, 7:481-484.
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1. Brock A, Krause S, Ingber DE. Control of cancer formation by intrinsic genetic noise and microenvironmental cues. Nat Rev Cancer, 2015, 15:499-509.
2. Nieto MA. The ins and outs of the epithelial to mesenchymal transition in health and disease. Annu Rev Cell Dev Biol, 2011, 27:347-376.
3. Kise K, Kinugasa-Katayama Y, Takakura N. Tumor microenvironment for cancer stem cells. Adv Drug Deliv Rev, 2016, 99:197-205.
4. Bedogni B, Welford SM, Cassarino DS, et al. The hypoxic microenvironment of the skin contributes to Akt-mediated melanocyte transformation. Cancer Cell, 2005, 8:443-454.
5. Ballas LK, Hu BR, Quinn DI. Chromoplexy and hypoxic microenvironment drives prostate cancer. Lancet Oncol, 2014, 15:1419-1421.
6. Higgins DF, Kimura K, Bernhardt WM, et al. Hypoxia promotes fibrogenesis in vivo via HIF-1 stimulation of epithelial-to-mesenchymal transition. J Clin Invest, 2007, 117:3810-3820.
7. Bartis D, Mise N, Mahida RY, et al. Epithelial-mesenchymal transition in lung development and disease:does it exist and is it important? Thorax, 2014, 69:760-765.
8. Rho JK, Choi YJ, Lee JK, et al. Epithelial to mesenchymal transition derived from repeated exposure to gefitinib determines the sensitivity to EGFR inhibitors in A549, a non-small cell lung cancer cell line. Lung Cancer, 2009, 63:219-226.
9. Shintani Y, Okimura A, Sato K, et al. Epithelial to mesenchymal transition is a determinant of sensitivity to chemoradiotherapy in non-small cell lung cancer. Ann Thorac Surg, 2011, 92:1794-1804.
10. Nicolini A, Ferrari P, Fini M, et al. Chemoresistance to paclitaxel induces epithelial mesenchymal transition and enhances metastatic potential for epithelial ovarian carcinoma cells. Int J Oncol, 2007, 31:277-283.
11. Sulzer MA, Leers MP, van Noord JA, et al. Reduced E-cadherin expression is associated with increased lymph node metastasis and unfavorable prognosis in non-small cell lung cancer. Am J Respir Crit Care Med, 1998, 157:1319-1323.
12. Dauphin M, Barbe C, Lemaire S, et al. Vimentin expression predictsthe occurrence of metastases in non-small cell lung carcinomas. Lung Cancer, 2013, 81:117-122.
13. 方美玉.进展期非小细胞肺癌药物治疗进展.中国呼吸与危重监护杂志, 2008, 7:481-484.
14. Rho JK, Choi YJ, Lee JK, et al. Epithelial to mesenchymal transition derived from repeated exposure to gefitinib determines the sensitivity to EGFR inhibitors in A549, a non-small cell lung cancer cell line. Lung Cancer, 2009, 63:219-226.
15. Shintani Y, Okimura A, Sato K, et al. Epithelial to mesenchymal transition is a determinant of sensitivity to chemoradiotherapy in non-small cell. Ann Thorac Surg, 2011, 92:1794.

Chinese Journal of Respiratory and Critical Care Medicine

The Influence of Hypoxia Microenvironment on Metastasis Induced by Epithelial-Mesenchymal Transition of Human Lung Adenocarcinoma

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