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去细胞化的乳腺基质作为体外三维癌症培养的生物活性微环境。

Decellularized breast matrix as bioactive microenvironment for in vitro three-dimensional cancer culture.

机构信息

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.

出版信息

J Cell Physiol. 2019 Apr;234(4):3425-3435. doi: 10.1002/jcp.26782. Epub 2018 Nov 1.

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.

摘要

乳腺癌(BC)是导致女性癌症相关死亡的主要原因,其生存率不理想。对乳腺癌遗传基础的认识的进步为开发能够治疗转移性疾病的基因药物提供了机会。在这里,我们首先展示了从脱细胞人活检组织开始应用于正常乳腺和乳腺癌细胞外基质(ECM)的高效组织工程方法,使用十二烷基醚硫酸钠溶液生成具有三维(3D)生物活性的模型。脱细胞组织通过组织学和 ECM 成分分析,从组织中最大限度地去除遗传成分,对 ECM 结构和天然成分的损伤最小。重要的是,我们证明了 3D ECM 保留了组织的生物学特性。我们证明,在 MCF-7 细胞(人乳腺癌腺癌细胞系)进行 30 天再细胞化后,3D 癌症 ECM 诱导上皮-间充质转化(EMT)和癌症增殖的过度表达。同时,来自乳房的正常 ECM 通过诱导细胞凋亡抑制 EMT 和细胞生长。鉴于脱细胞后 ECM 中保留的生物学活性,我们相信这些方法是未来用于 BC 和乳房发育的临床前研究的有力工具。

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