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Development of a Novel Highly Spontaneous Metastatic Model of Esophageal Squamous Cell Carcinoma Using Renal Capsule Technology

Authors Gao P, Liu H, Yang Z, Hui Y, Shi Z, Yang Z, Song M, Yao M, Fan W, Yang J, Hao Y, Fan T

Received 5 November 2020

Accepted for publication 13 January 2021

Published 4 February 2021 Volume 2021:14 Pages 785—793

DOI https://doi.org/10.2147/OTT.S290564

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Federico Perche


Pan Gao,1,2,* Hongtao Liu,3,* Zhenzhen Yang,1,2 Yiran Hui,2,4 Zhuangzhuang Shi,2 Zhen Yang,2 Min Song,2 Menghui Yao,2 Wenfei Fan,1 Jinhua Yang,1 Yibin Hao,1 Tianli Fan2

1People’s Hospital of Zhengzhou, Zhengzhou, Henan, 450001, People’s Republic of China; 2Department of Pharmacology, School of Basic Medicine, Zhengzhou University, Zhengzhou, Henan, 450001, People’s Republic of China; 3Laboratory for Cell Biology, College of Life Sciences of Zhengzhou University, Zhengzhou, Henan, 450001, People’s Republic of China; 4University of Chinese Academy of Sciences-Shenzhen Hospital, Shenzhen, Guangdong, 518106, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Tianli Fan
Department of Pharmacology, School of Basic Medicine, Zhengzhou University, Zhengzhou, Henan, 450001, People’s Republic of China
Email fantianli@zzu.edu.cn

Purpose: Increasing evidence has demonstrated that animal models are imperative to investigate the potential molecular mechanism of metastasis and discover anti-metastasis drugs; however, efficient animal models to unveil the underlying mechanisms of metastasis in esophageal squamous cell carcinoma (ESCC) are limited.
Methods: ESCC cell EC9706 with high invasiveness was screened by repeated Transwell assays. Its biological characteristics were identified by flow cytometry as well as by the wound healing and CCK-8 assays. Besides, the levels of epithelial–mesenchymal transition-related markers were examined using Western blotting. Parental (EC9706-I0) and subpopulation (EC9706-I3) cells were employed to establish the renal capsule model. Next, the tumor growth was detected by a live animal imaging system, and hematoxylin and eosin staining was applied to evaluate the metastatic status in ESCC.
Results: EC9706-I3 cells showed rapid proliferation ability, S phase abundance, and high invasive ability; obvious upregulation in N-cadherin, Snail, Vimentin, and Bit1; and downregulation in E-cadherin. EC9706-I3 cells were less sensitive to the chemotherapy drug 5-fluorouracil than EC9706-I0 cells; however, both cell lines reached a tumorigenesis rate of 100% in the renal capsule model. The live animal imaging system revealed that the tumors derived from EC9706-I0 cells grew more slowly than those from EC9706-I3 cells at weeks 3– 14. The EC9706-I3 xenograft model displayed a spontaneous metastatic site, including kidney, heart, liver, lung, pancreas, and spleen, with a distant metastatic rate of 80%.
Conclusion: Our data suggested that the metastatic model was successfully established, providing a novel platform for further exploring the molecular mechanisms of metastasis in ESCC patients.

Keywords: esophageal squamous cell carcinoma, renal capsule model, spontaneous metastasis, epithelial–mesenchymal transition process

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