TGF-\u03b21 stimulates epithelial\u2013mesenchymal transition and cancer-associated myoepithelial cell during the progression from in situ to invasive breast cancer

Li Wang,Fang Liu,Qingxiang Meng,Shuling Wang,Cong Xu,Jiao Jiao,Jing Liu,Xia Liu,Yang Yang,Lu Cao,Guomin Xiang,Yun Niu

doi:10.1186/s12935-019-1068-7

Abstract

BackgroundThe 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.MethodsEMT 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.ResultsWe 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.ConclusionsIn conclusion, these findings demonstrated that both EMT phenotypes and cancer-associated myoepithelial cells may have an impact on the development of invasive breast cancer.

Highlights

Ductal carcinoma in situ (DCIS) is recognized as a localized tumor cell proliferation in the ductal-lobular system that does not penetrate the basement membrane and has the potential to transform into invasive breast cancer [1]
Invasive lobular carcinomas were not included in this study as they are characterized by loss of E-cadherin
Martinez et al recorded that medium conditioned with malignant epithelial cell was able to induce myoepithelial cell fibroblast growth factor 2 (FGF2) secretion that supports carcinogenesis [27], Our results suggest that transforming growth factor-β (TGF-β1) increases MDA-MB-231 migration, invasion and cytokines secretion when co-cultured with MCF-7

Summary

Introduction

Ductal carcinoma in situ (DCIS) is recognized as a localized tumor cell proliferation in the ductal-lobular system that does not penetrate the basement membrane and has the potential to transform into invasive breast cancer [1]. EMT occurs when epithelial cells acquire mesenchymal properties such as cytoskeleton reorganization, loss of cell polarity and breakdown of cell junctions—all of which lead to increased cell motility [4, 5] Besides carcinogenesis, this process has been demonstrated in tissue regeneration and wound healing [6]. This process has been demonstrated in tissue regeneration and wound healing [6] Both local and disseminated tumor metastasis have been thought to be a product of the EMT, as this process bestows otherwise benign cells with the properties to escape the rigid constraints of the surrounding tissue architecture, such as the basement membrane. This paper explored the relationship and potential mechanism between myoepithelial cells and EMT-associated genes in facilitating the transformation from DCIS to breast cancer

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Results

Discussion

Conclusion