Abstract P4-16-07: Mesenchymal-epithelial transition (MET) and epithelial-mesenchymal transition (EMT) are closely related to chemotherapy resistance of triple negative breast cancer

Abstract

Abstract Triple negative breast cancer (TNBC) is among the most aggressive clinical phenotypes and the presence of residual resistant cancer cells of TNBC after chemotherapy is associated with tumor recurrence and metastasis. In recent years more and more evidence highlight a crucial role of CD44 (+)/CD24 (-/low) (stem/progenitor cell-phenotype) population in cancer drug resistance but the mechanism remains elusive. In the current study, we screened for CD44 and CD24 using Fluorescence-activated cell sorting (FACS) in 8 TNBC cell lines before and after Docetaxel and Doxorubicin treatment. Our data showed that after Docetaxel treatment, several CD44 (+)/CD24 (-/low) cell lines changed their phenotypes to CD44 (+)/CD24 (+) and most of the CD44 (+)/CD24 (+) cell lines kept their double positive phenotypes. In contrast, after Doxorubicin treatment, all the CD44 (+)/CD24 (-/low) cell lines kept their phenotypes and all the CD44 (+)/CD24 (+) cell lines changed their phenotypes to CD44 (+)/CD24 (-/low). Furthermore, among the studied 8 cell lines, CD44 (+)/CD24 (+) cell population is always more resistant to Docetaxel and CD44 (+)/CD24 (-/low) population is always more resistant to Doxorubicin. Our finding of EMT transition from CD44 (+)/CD24 (+) to CD44 (+)/CD24 (-/low) in breast cancer cell lines and its inducible by Doxorubicin is consistent with the literature. However, our results showed for the first time that both EMT and the inverse MET in TNBC could be induced by specific chemotherapy drugs based on the phenotypes of CD44 and CD24. Besides, our gene microarray data also showed that TGFb2, BCL2, KLF6 and TAF4 pathways were dramatically changed in both CD44 (+)/CD24 (+) to CD44 (+)/CD24 (-/low) transition and CD44 (+)/CD24 (-/low) to CD44 (+)/CD24 (+) transition. Further study of these pathways in the transitions may give us new clues to overcome the chemotherapy resistance and lead us to develop successful therapeutic strategies of different types of TNBC. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-16-07.