Frank-Kamenetskii Anastasia, Mook Julia, Reeves Meredith, Boulanger Corinne A, Meyer Thomas J, Ragle Lauren, Jordan H Caroline, Smith Gilbert H, Booth Brian W
Department of Bioengineering, Clemson University, Clemson, SC, USA.
Department of Biological Sciences, Clemson University, Clemson, SC, USA.
Oncotarget. 2020 Jul 28;11(30):2919-2929. doi: 10.18632/oncotarget.27679.
The influence of breast cancer cells on normal cells of the microenvironment, such as fibroblasts and macrophages, has been heavily studied but the influence of normal epithelial cells on breast cancer cells has not. Here using and models we demonstrate the impact epithelial cells and the mammary microenvironment can exert on breast cancer cells. Under specific conditions, signals that originate in epithelial cells can induce phenotypic and genotypic changes in cancer cells. We have termed this phenomenon "cancer cell redirection." Once breast cancer cells are redirected, either or , they lose their tumor forming capacity and undergo a genetic expression profile shift away from one that supports a cancer profile towards one that supports a non-tumorigenic epithelial profile. These findings indicate that epithelial cells and the normal microenvironment influence breast cancer cells and that under certain circumstances restrict proliferation of tumorigenic cells.
乳腺癌细胞对微环境中的正常细胞（如成纤维细胞和巨噬细胞）的影响已得到大量研究，但正常上皮细胞对乳腺癌细胞的影响却未被研究。在此，我们使用[具体模型1]和[具体模型2]模型，证明上皮细胞和乳腺微环境可对乳腺癌细胞产生影响。在特定条件下，源自上皮细胞的信号可诱导癌细胞发生表型和基因型变化。我们将此现象称为“癌细胞重定向”。一旦乳腺癌细胞发生重定向，无论是[重定向方式1]还是[重定向方式2]，它们都会失去肿瘤形成能力，并经历基因表达谱的转变，从支持癌症特征的谱型转变为支持非致瘤性上皮特征的谱型。这些发现表明，上皮细胞和正常微环境会影响乳腺癌细胞，并且在某些情况下会限制致瘤细胞的增殖。
