Abstract B02: Intratumoral bidirectional transitions between epithelial and mesenchymal cells in triple-negative breast cancer

Abstract

Abstract Epithelial-mesenchymal transition (EMT) and its reverse process, MET, are crucial in cancer metastasis. EMT allows cancer cells to move to proximal blood vessels for intravasation. However, because EMT and MET processes are dynamic, mesenchymal cancer cells are likely to undergo MET to form metastatic foci and subsequently re-undergo EMT to restart the metastatic process. To elucidate such regulation, we chose HCC38, a human triple-negative breast cancer (TNBC) cell line, because HCC38 is composed of epithelial and mesenchymal populations. We purified epithelial and mesenchymal cells from Venus-labeled and unlabeled HCC38 and mixed them at various ratios to follow EMT and MET. Using this system, we demonstrate that the two populations significantly enhance the transition of cells from the other population to their own. In addition, knockdown of ZEB1 or SLUG significantly suppressed EMT but promoted partial MET. We also demonstrate that primary breast cancer cells underwent EMT. These changes were very similar to those observed in EMT in HCC38. Consequently, we propose HCC38 as a suitable model to analyze EMT-MET dynamics that could affect development of TNBC. Citation Format: Mizuki Yamamoto, Jun-ichiro Inoue. Intratumoral bidirectional transitions between epithelial and mesenchymal cells in triple-negative breast cancer [abstract]. In: Proceedings of the AACR Special Conference: Advances in Breast Cancer Research; 2017 Oct 7-10; Hollywood, CA. Philadelphia (PA): AACR; Mol Cancer Res 2018;16(8_Suppl):Abstract nr B02.