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

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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.	许成云, 倪庆桂, 张陆勇. 肿瘤微环境与肿瘤血管新生. 中国医疗前沿: 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.	殷晓丽, 刘兆玉. 上皮间质转化在肿瘤中的研究进展. 医学综述, 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.	张彦璐, 陈影, 应国清. 上皮间质转化在肿瘤侵袭转移中的研究进展. 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.	贾皑, 张璐, 任莉, 等. EMT 分子标志物在肝癌细胞系中的表达及其意义. 西安交通大学学报: 医学版, 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.	沈良华, 吴璐华, 张仙丽, 等. PTBP1 通过 EMT 途径促进肝癌细胞的迁移与侵袭. 中国病理生理杂志, 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.	董保龙, 韩彩文, 史明, 等. 波形蛋白在肝细胞癌中的研究进展. 基础医学与临床, 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.	张霞, 李惠萍. 上皮间质转化的分子标志物. 国际呼吸杂志, 2012, 32(17): 1358-1361.
26.	徐晓强, 郭佳, 关锋. 膀胱癌细胞 YTS-1 的条件培养基诱导膀胱上皮细胞 HCV29 发生上皮间质转化和糖链表达变化. 生物学杂志, 2018, 35(5): 23-27.
27.	谢雨潇, 廖锐, 潘龙, 等. 肝星状细胞条件培养基激活 ERK1/2 通路诱导肝癌细胞增殖及上皮间质转化. 细胞与分子免疫学杂志, 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.	雒强. CAF 来源的 exosome 促进前列腺癌细胞上皮间质转化. 天津: 天津医科大学, 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. 许成云, 倪庆桂, 张陆勇. 肿瘤微环境与肿瘤血管新生. 中国医疗前沿: 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. 殷晓丽, 刘兆玉. 上皮间质转化在肿瘤中的研究进展. 医学综述, 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. 张彦璐, 陈影, 应国清. 上皮间质转化在肿瘤侵袭转移中的研究进展. 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. 贾皑, 张璐, 任莉, 等. EMT 分子标志物在肝癌细胞系中的表达及其意义. 西安交通大学学报: 医学版, 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. 沈良华, 吴璐华, 张仙丽, 等. PTBP1 通过 EMT 途径促进肝癌细胞的迁移与侵袭. 中国病理生理杂志, 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. 董保龙, 韩彩文, 史明, 等. 波形蛋白在肝细胞癌中的研究进展. 基础医学与临床, 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. 张霞, 李惠萍. 上皮间质转化的分子标志物. 国际呼吸杂志, 2012, 32(17): 1358-1361.
26. 徐晓强, 郭佳, 关锋. 膀胱癌细胞 YTS-1 的条件培养基诱导膀胱上皮细胞 HCV29 发生上皮间质转化和糖链表达变化. 生物学杂志, 2018, 35(5): 23-27.
27. 谢雨潇, 廖锐, 潘龙, 等. 肝星状细胞条件培养基激活 ERK1/2 通路诱导肝癌细胞增殖及上皮间质转化. 细胞与分子免疫学杂志, 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. 雒强. CAF 来源的 exosome 促进前列腺癌细胞上皮间质转化. 天津: 天津医科大学, 2018.

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