TGF-β induced epithelial-mesenchymal transition in an advanced cervical tumor model by 3D printing

被引：46
作者：
Pang, Y. [1 ,2 ,3 ]
Mao, S. S. [1 ,2 ,3 ]
Yao, R. [1 ,2 ,3 ]
He, J. Y. [1 ,2 ,3 ]
Zhou, Z. Z. [1 ,2 ,3 ]
Feng, L. [4 ,5 ]
Zhang, K. T. [4 ,5 ]
Cheng, S. J. [4 ,5 ]
Sun, W. [1 ,2 ,3 ,6 ]
机构：
[1] Tsinghua Univ, Dept Mech Engn, Biomfg Ctr, Beijing 100084, Peoples R China
[2] Biomfg & Rapid Forming Technol Key Lab Beijing, Beijing 100084, Peoples R China
[3] Tsinghua Univ, Overseas Expertise Intro Ctr Discipline Innovat, Beijing 100084, Peoples R China
[4] Chinese Acad Med Sci, State Key Lab Mol Oncol, Natl Canc Ctr, Canc Hosp, Beijing 100021, Peoples R China
[5] Peking Union Med Coll, Beijing 100021, Peoples R China
[6] Drexel Univ, Dept Mech Engn, Philadelphia, PA 19104 USA
来源：
BIOFABRICATION | 2018年 / 10卷 / 04期
基金：
北京市自然科学基金; 中国国家自然科学基金;
关键词：
epithelial-mesenchymal transition; 3D printing; cervical tumor metastasis; TGF-beta; HeLa cell; CANCER PROGRESSION; EMT; GROWTH; SNAIL; MICROENVIRONMENT; EXPRESSION; CARCINOMA; THERAPY;
D O I：
10.1088/1758-5090/aadbde
中图分类号：
R318 [生物医学工程];
学科分类号：
0831 ;
摘要：
An advanced in vitro cervical tumor model was established by 3D printing to study the epithelial-to-mesenchymal transition (EMT), which is a very important stage of dissemination of carcinoma leading to metastatic tumors. A HeLa/hydrogel grid construct composed of gelatin, alginate, Matrigel and HeLa cells was fabricated by forced extrusion in a layer-by-layer fashion. HeLa cells rapidly proliferated, formed spheroids and presented tumorigenic characteristic in the 3D-printed structure. With the supplement of TGF-beta, aggregated HeLa cells started to disintegrate, and some of them changed into fibroblast-like spindle morphology, which indicated that EMT was induced. The downregulation of epithelial marker E-cadherin, and up-regulation of mesenchymal markers such as snail, vimentin and N-cadherin were all observed in the 3D-printed model, and performed differently in 3D and 2D models. The TGF-beta induced EMT was inhibited by the treatment of disulfiram and EMT pathway inhibitor C19 in a dose dependent manner, showing great potential for future studies of a therapeutic program towards cervical tumor metastasis.
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页数：12
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