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

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

doi:10.1186/s12935-019-1068-7

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.

Authors

Li Wang^#^{1

2}, Cong Xu^#^{1

3}, Xia Liu⁴, Yang Yang^{1

3}, Lu Cao^{1

3}, Guomin Xiang^{1

3}, Fang Liu^{1

3}, Shuling Wang^{1

5}, Jing Liu^{1

3}, Qingxiang Meng^{1

3}, Jiao Jiao^{1

3}, Yun Niu^{1

3}

Affiliations

¹ Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Key Laboratory of Cancer Prevention and Therapy, West Huanhu Road, Ti Yuan Bei, Hexi District, Tianjin, 300060 China.
² 2The Second Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060 China.
³ 3Department of Breast Cancer Pathology and Research Laboratory, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060 China.
⁴ 5Department of Oncology, General Hospital of Tianjin Medical University, 154 Anshan Road, Heping District, Tianjin, 300052 China.
⁵ 4Department of Breast Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060 China.

^# Contributed equally.

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.