TGF-β1 stimulates epithelial-mesenchymal transition and cancer-associated myoepithelial cell during the progression from in situ to invasive breast cancer

Cancer Cell Int. 2019 Dec 19;19:343. doi: 10.1186/s12935-019-1068-7. eCollection 2019.

Abstract

Background: The progression of ductal carcinoma in situ (DCIS) into invasive ductal carcinoma (IDC) is prevented by normal breast myoepithelial cells. Studies have suggested that EMT-associated genes were enriched in IDC in contrast to DCIS. This paper explored the relationship and potential mechanism between myoepithelial cells and EMT-associated genes in facilitating the transformation from DCIS to breast cancer.

Methods: EMT markers and myoepithelial phenotypic markers in IDC, DCIS, and healthy breast tissue were characterized using immunohistochemical assay. Both in vivo and in vitro models were created to mimic the various cell-cell interactions in the development of invasive breast cancer.

Results: We found that EMT markers were more abundant in invasive carcinomas than DCIS and adjacent normal breast tissue. Meanwhile, TGF-β1 regulated the morphology of MCF-7 (epithelial cells substitute) migration and EMT markers during the transformation from DCIS to invasive breast cancer. Additionally, TGF-β1 also regulated invasion, migration and cytokines secretion of MDA-MB-231 (myoepithelial cells substitute) and epithelial cells when co-cultured with MCF-7 both in vitro and in vivo.

Conclusions: In conclusion, these findings demonstrated that both EMT phenotypes and cancer-associated myoepithelial cells may have an impact on the development of invasive breast cancer.

Keywords: DCIS; Epithelial–mesenchymal transition; Myoepithelial cell; Progression; TGF-β1.