Effect of conditioned medium of vascular endothelial cells on the epithelial-mesenchymal transition of hepatocellular carcinoma cells_Journal of Biomedical Engineering

Authors：

XU Bowen , HE Jia , GAO Wenbo , SU Guanyue , LIU Xiaoheng ,  SHEN Yang

Institute of Biomedical Engineering, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu 610041, P.R.China;

Corresponding?author：

SHEN Yang, Email: shenyang24@126.com

Keywords：

tumor microenvironment; tumor angiogenesis; epithelial-mesenchymal transition; indirect co-culture

DOI：

10.7507/1001-5515.201907041

Video：

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This study aims to investigate the effect of substances secreted or metabolized by vascular endothelial cells on epithelial-mesenchymal transition (EMT) of hepatocellular carcinoma cells under indirect co-culture condition. Human hepatocellular carcinoma cell line QGY-7703 was cultured in vitro, and then was co-cultured with conditioned medium of human umbilical vein endothelial cells (HUVEC). The morphological changes of QGY-7703 cells were observed by inverted phase contrast microscopy. The migration ability of QGY-7703 cells was analyzed by scratch-wound assays. The effect of conditioned medium on the expression and distribution of EMT related proteins was detected by Western blot and immunofluorescence assays, respectively. The results showed that the QGY-7703 cells gradually changed from polygonal to spindle shape, the migration ability promoted significantly, and both the expression and distribution of EMT related marker changed in a time-dependent manner after co-culturing. The results confirm that vascular endothelial cells can induce EMT in hepatocellular carcinoma cells under indirect co-culture condition.

Citation： XU Bowen, HE Jia, GAO Wenbo, SU Guanyue, LIU Xiaoheng, SHEN Yang. Effect of conditioned medium of vascular endothelial cells on the epithelial-mesenchymal transition of hepatocellular carcinoma cells. Journal of Biomedical Engineering, 2020, 37(3): 442-449. doi: 10.7507/1001-5515.201907041 Copy

1.	Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
2.	Zeng Dongqiang, Li Meiyi, Zhou Rui, et al. Tumor microenvironment characterization in gastric cancer identifies prognostic and immunotherapeutically relevant gene signatures. Cancer Immunol Res, 2019, 7(5): 737-750.
3.	Chandler K B, Costello C E, Rahimi N. Glycosylation in the tumor microenvironment: implications for tumor angiogenesis and metastasis. Cells, 2019, 8(6): 544.
4.	許成云, 倪慶桂, 張陸勇. 腫瘤微環境與腫瘤血管新生. 中國醫療前沿: 上半月, 2009, 4(5): 21-23, 90.
5.	Shojaei F. Anti-angiogenesis therapy in cancer: Current challenges and future perspectives. Cancer Lett, 2012, 320(2): 130-137.
6.	Cheng X K, Lin W R, Jiang H, et al. MicroRNA-129-5p inhibits invasiveness and metastasis of lung cancer cells and tumor angiogenesis via targeting VEGF. Eur Rev Med Pharmaco, 2019, 23(7): 2827-2837.
7.	Mirzaei S, Baghaei K, Parivar K, et al. The expression level changes of microRNAs 200a/205 in the development of invasive properties in gastric cancer cells through epithelial-mesenchymal transition. Eur J Pharmacol, 2019, 857: 172426.
8.	殷曉麗, 劉兆玉. 上皮間質轉化在腫瘤中的研究進展. 醫學綜述, 2017, 23(12): 2359-2363, 2369.
9.	Assani G, Zhou Yunfeng. Effect of modulation of epithelial-mesenchymal transition regulators Snail1 and Snail2 on cancer cell radiosensitivity by targeting of the cell cycle, cell apoptosis and cell migration/invasion. Oncol Lett, 2019, 17(1): 23-30.
10.	張彥璐, 陳影, 應國清. 上皮間質轉化在腫瘤侵襲轉移中的研究進展. 浙江化工, 2019, 50(7): 11-15.
11.	Campbell K. Contribution of epithelial-mesenchymal transitions to organogenesis and cancer metastasis. Curr Opin Cell Biol, 2018, 55: 30-35.
12.	賈皚, 張璐, 任莉, 等. EMT 分子標志物在肝癌細胞系中的表達及其意義. 西安交通大學學報: 醫學版, 2019, 40(4): 537-541.
13.	Su Shan, Lin Xueyan, Ding Ning, et al. Effects of PARP-1 inhibitor and ERK inhibitor on epithelial mesenchymal transitions of the ovarian cancer SKOV3 cells. Pharmacol Rep, 2016, 68(6): 1225-1229.
14.	Sun Jingjing, Stathopoulos A. FGF controls epithelial-mesenchymal transitions during gastrulation by regulating cell division and apicobasal polarity. Development, 2018, 145(19): dev161927.
15.	Kalcheim C. Epithelial-mesenchymal transitions during neural crest and somite development. J Clin Med, 2015, 5(1): 1.
16.	Ding Qiang, Xia Yujia, Ding Shuping, et al. Potential role of CXCL9 induced by endothelial cells/CD133+ liver cancer cells co-culture system in tumor transendothelial migration. Genes Cancer, 2016, 7(7/8): 254-259.
17.	Kuang Youlin, He Weiyang, Liang Simin, et al. Prostaglandin E₂ inhibits prostate cancer progression by countervailing tumor microenvironment-induced impairment of dendritic cell migration through LXR alpha/CCR7 pathway. J Immunol Res, 2018, 2018: 5808962.
18.	Lacal P M, Graziani G. Therapeutic implication of vascular endothelial growth factor receptor-1(VEGFR-1) targeting in cancer cells and tumor microenvironment by competitive and non-competitive inhibitors. Pharmacol Res, 2018, 136: 97-107.
19.	Costanza B, Rademaker G, Tiamiou A, et al. Transforming growth factor beta-induced, an extracellular matrix interacting protein, enhances glycolysis and promotes pancreatic cancer cell migration. Int J Cancer, 2019, 145(6): 1570-1584.
20.	沈良華, 吳璐華, 張仙麗, 等. PTBP1 通過 EMT 途徑促進肝癌細胞的遷移與侵襲. 中國病理生理雜志, 2019, 35(10): 1819-1825.
21.	Ye Zhiyu, Chen Xudong, Chen Xiaogang. ARK5 promotes invasion and migration in hepatocellular carcinoma cells by regulating epithelial-mesenchymal transition. Oncol Lett, 2018, 15(2): 1511-1516.
22.	Zuo Jianhong, Wen Juan, Lei Mingsheng, et al. Hypoxia promotes the invasion and metastasis of laryngeal cancer cells via EMT. Med Oncol, 2016, 33(2): 15.
23.	董保龍, 韓彩文, 史明, 等. 波形蛋白在肝細胞癌中的研究進展. 基礎醫學與臨床, 2020, 40(2): 238-242.
24.	Rawal P, Siddiqui H, Hassan M, et al. Endothelial cell-derived TGF-beta promotes epithelial-mesenchymal transition via CD133 in HBx-infected hepatoma cells. Front Oncol, 2019, 9: 308.
25.	張霞, 李惠萍. 上皮間質轉化的分子標志物. 國際呼吸雜志, 2012, 32(17): 1358-1361.
26.	徐曉強, 郭佳, 關鋒. 膀胱癌細胞 YTS-1 的條件培養基誘導膀胱上皮細胞 HCV29 發生上皮間質轉化和糖鏈表達變化. 生物學雜志, 2018, 35(5): 23-27.
27.	謝雨瀟, 廖銳, 潘龍, 等. 肝星狀細胞條件培養基激活 ERK1/2 通路誘導肝癌細胞增殖及上皮間質轉化. 細胞與分子免疫學雜志, 2017, 33(2): 210-214, 219.
28.	Zhuang J, Lu Q, Shen B, et al. TGFbeta1 secreted by cancer-associated fibroblasts induces epithelial-mesenchymal transition of bladder cancer cells through lncRNA-ZEB2NAT. Sci Rep, 2015, 5: 11924.
29.	雒強. CAF 來源的 exosome 促進前列腺癌細胞上皮間質轉化. 天津: 天津醫科大學, 2018.

1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
2. Zeng Dongqiang, Li Meiyi, Zhou Rui, et al. Tumor microenvironment characterization in gastric cancer identifies prognostic and immunotherapeutically relevant gene signatures. Cancer Immunol Res, 2019, 7(5): 737-750.
3. Chandler K B, Costello C E, Rahimi N. Glycosylation in the tumor microenvironment: implications for tumor angiogenesis and metastasis. Cells, 2019, 8(6): 544.
4. 許成云, 倪慶桂, 張陸勇. 腫瘤微環境與腫瘤血管新生. 中國醫療前沿: 上半月, 2009, 4(5): 21-23, 90.
5. Shojaei F. Anti-angiogenesis therapy in cancer: Current challenges and future perspectives. Cancer Lett, 2012, 320(2): 130-137.
6. Cheng X K, Lin W R, Jiang H, et al. MicroRNA-129-5p inhibits invasiveness and metastasis of lung cancer cells and tumor angiogenesis via targeting VEGF. Eur Rev Med Pharmaco, 2019, 23(7): 2827-2837.
7. Mirzaei S, Baghaei K, Parivar K, et al. The expression level changes of microRNAs 200a/205 in the development of invasive properties in gastric cancer cells through epithelial-mesenchymal transition. Eur J Pharmacol, 2019, 857: 172426.
8. 殷曉麗, 劉兆玉. 上皮間質轉化在腫瘤中的研究進展. 醫學綜述, 2017, 23(12): 2359-2363, 2369.
9. Assani G, Zhou Yunfeng. Effect of modulation of epithelial-mesenchymal transition regulators Snail1 and Snail2 on cancer cell radiosensitivity by targeting of the cell cycle, cell apoptosis and cell migration/invasion. Oncol Lett, 2019, 17(1): 23-30.
10. 張彥璐, 陳影, 應國清. 上皮間質轉化在腫瘤侵襲轉移中的研究進展. 浙江化工, 2019, 50(7): 11-15.
11. Campbell K. Contribution of epithelial-mesenchymal transitions to organogenesis and cancer metastasis. Curr Opin Cell Biol, 2018, 55: 30-35.
12. 賈皚, 張璐, 任莉, 等. EMT 分子標志物在肝癌細胞系中的表達及其意義. 西安交通大學學報: 醫學版, 2019, 40(4): 537-541.
13. Su Shan, Lin Xueyan, Ding Ning, et al. Effects of PARP-1 inhibitor and ERK inhibitor on epithelial mesenchymal transitions of the ovarian cancer SKOV3 cells. Pharmacol Rep, 2016, 68(6): 1225-1229.
14. Sun Jingjing, Stathopoulos A. FGF controls epithelial-mesenchymal transitions during gastrulation by regulating cell division and apicobasal polarity. Development, 2018, 145(19): dev161927.
15. Kalcheim C. Epithelial-mesenchymal transitions during neural crest and somite development. J Clin Med, 2015, 5(1): 1.
16. Ding Qiang, Xia Yujia, Ding Shuping, et al. Potential role of CXCL9 induced by endothelial cells/CD133+ liver cancer cells co-culture system in tumor transendothelial migration. Genes Cancer, 2016, 7(7/8): 254-259.
17. Kuang Youlin, He Weiyang, Liang Simin, et al. Prostaglandin E₂ inhibits prostate cancer progression by countervailing tumor microenvironment-induced impairment of dendritic cell migration through LXR alpha/CCR7 pathway. J Immunol Res, 2018, 2018: 5808962.
18. Lacal P M, Graziani G. Therapeutic implication of vascular endothelial growth factor receptor-1(VEGFR-1) targeting in cancer cells and tumor microenvironment by competitive and non-competitive inhibitors. Pharmacol Res, 2018, 136: 97-107.
19. Costanza B, Rademaker G, Tiamiou A, et al. Transforming growth factor beta-induced, an extracellular matrix interacting protein, enhances glycolysis and promotes pancreatic cancer cell migration. Int J Cancer, 2019, 145(6): 1570-1584.
20. 沈良華, 吳璐華, 張仙麗, 等. PTBP1 通過 EMT 途徑促進肝癌細胞的遷移與侵襲. 中國病理生理雜志, 2019, 35(10): 1819-1825.
21. Ye Zhiyu, Chen Xudong, Chen Xiaogang. ARK5 promotes invasion and migration in hepatocellular carcinoma cells by regulating epithelial-mesenchymal transition. Oncol Lett, 2018, 15(2): 1511-1516.
22. Zuo Jianhong, Wen Juan, Lei Mingsheng, et al. Hypoxia promotes the invasion and metastasis of laryngeal cancer cells via EMT. Med Oncol, 2016, 33(2): 15.
23. 董保龍, 韓彩文, 史明, 等. 波形蛋白在肝細胞癌中的研究進展. 基礎醫學與臨床, 2020, 40(2): 238-242.
24. Rawal P, Siddiqui H, Hassan M, et al. Endothelial cell-derived TGF-beta promotes epithelial-mesenchymal transition via CD133 in HBx-infected hepatoma cells. Front Oncol, 2019, 9: 308.
25. 張霞, 李惠萍. 上皮間質轉化的分子標志物. 國際呼吸雜志, 2012, 32(17): 1358-1361.
26. 徐曉強, 郭佳, 關鋒. 膀胱癌細胞 YTS-1 的條件培養基誘導膀胱上皮細胞 HCV29 發生上皮間質轉化和糖鏈表達變化. 生物學雜志, 2018, 35(5): 23-27.
27. 謝雨瀟, 廖銳, 潘龍, 等. 肝星狀細胞條件培養基激活 ERK1/2 通路誘導肝癌細胞增殖及上皮間質轉化. 細胞與分子免疫學雜志, 2017, 33(2): 210-214, 219.
28. Zhuang J, Lu Q, Shen B, et al. TGFbeta1 secreted by cancer-associated fibroblasts induces epithelial-mesenchymal transition of bladder cancer cells through lncRNA-ZEB2NAT. Sci Rep, 2015, 5: 11924.
29. 雒強. CAF 來源的 exosome 促進前列腺癌細胞上皮間質轉化. 天津: 天津醫科大學, 2018.

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