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Decellularized breast matrix as bioactive microenvironment for in vitro three-dimensional cancer culture
Authors:Qin Jin  Gang Liu  Shubin Li  Haihan Yuan  Zhizhong Yun  Wenqi Zhang  Shu Zhang  Yanfeng Dai  Yuzhen Ma
Affiliation:1. State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Science, Inner Mongolia University, Hohhot, Inner Mongolia, China

Department of Pathology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China

Qin Jin, Gang Liu, and Shubin Li contributed equally to this study.;2. State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Science, Inner Mongolia University, Hohhot, Inner Mongolia, China;3. State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Science, Inner Mongolia University, Hohhot, Inner Mongolia, China

Qin Jin, Gang Liu, and Shubin Li contributed equally to this study.;4. Department of Obstetrics, People's Hospital of Beijing Daxing District, Beijing, China;5. Centre of Reproductive Medicine, Inner Mongolia Hospital, Hohhot, Inner Mongolia, China;6. College of Basic Medical, Wanna Medical School, Wuhu, China;7. Department of Pathology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China

Abstract:Breast cancer (BC) is a leading cause of cancer-related death in women with unsatisfactory survival rates. Advances in the understanding of the genetic basis of BC provide the opportunity to develop gene-based medicines capable of treating metastatic diseases. Here, we first demonstrated efficient tissue engineering approaches applied to normal breast and BC extracellular matrix (ECM) starting from decellularized human biopsies to generate a three-dimensional (3D) bioactive model with the sodium lauryl ether sulfate solution. The decellularized tissues maximized the genetic component removal from tissues and minimally injured ECM structures and native compositions by histology and ECM compositions analyses. Importantly, we proved that the 3D ECM retained tissues biological properties. We demonstrated that after 30 days of recellularization with MCF-7 cell (human breast adenocarcinoma cell line), the 3D cancer ECM induced an overexpression of epithelial–mesenchymal transition (EMT) and cancer proliferation. Meanwhile, normal ECM from the breast inhibited EMT and cell growth with the inducement of apoptosis. Given the biological activity preserved in the ECM after decellularization, we believe these approaches are powerful tools for future preclinical research for BC and breast development.
Keywords:breast cancer (BC)  decellularized scaffold  extracellular matrix (ECM)  three-dimensional (3D) in vitro culture, tumor microenvironment
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