Details

Autor(en) / Beteiligte

• Yamamoto, Mizuki
• Sakane, Kota
• Tominaga, Kana
• Gotoh, Noriko
• Niwa, Takayoshi
• Kikuchi, Yasuko
• Tada, Keiichiro
• Goshima, Naoki
• Semba, Kentaro
• Inoue, Jun‐ichiro

Titel

Intratumoral bidirectional transitions between epithelial and mesenchymal cells in triple‐negative breast cancer

Ist Teil von

• Cancer science, 2017-06, Vol.108 (6), p.1210-1222

Ort / Verlag

England: John Wiley & Sons, Inc

Erscheinungsjahr

2017

Link zum Volltext

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• Epithelial–mesenchymal transition (EMT) and its reverse process, mesenchymal–epithelial transition MET, are crucial in several stages of cancer metastasis. Epithelial–mesenchymal transition 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 transiently and subsequently re‐undergo EMT to restart the metastatic process. Therefore, spatiotemporally coordinated mutual regulation between EMT and MET could occur during metastasis. To elucidate such regulation, we chose HCC38, a human triple‐negative breast cancer cell line, because HCC38 is composed of epithelial and mesenchymal populations at a fixed ratio even though mesenchymal cells proliferate significantly more slowly than epithelial cells. We purified epithelial and mesenchymal cells from Venus‐labeled and unlabeled HCC38 cells and mixed them at various ratios to follow EMT and MET. Using this system, we found that the efficiency of EMT is approximately an order of magnitude higher than that of MET and that the two populations significantly enhance the transition of cells from the other population to their own. In addition, knockdown of Zinc finger E‐box‐binding homeobox 1 (ZEB1) or Zinc finger protein SNAI2 (SLUG) significantly suppressed EMT but promoted partial MET, indicating that ZEB1 and SLUG are crucial to EMT and MET. We also show that primary breast cancer cells underwent EMT that correlated with changes in expression profiles of genes determining EMT status and breast cancer subtype. These changes were very similar to those observed in EMT in HCC38 cells. Consequently, we propose HCC38 as a suitable model to analyze EMT–MET dynamics that could affect the development of triple‐negative breast cancer. Triple negative breast cancer cell line HCC38 composed of epithelial and mesenchymal population at fixed ratio even though mesenchymal cells proliferate significantly slower than epithelial cells. Using this system, we demonstrate that the efficiency of EMT is about a magnitude higher than that of MET and that the two populations significantly enhance the transition of another population to own population. We propose that HCC38 is a suitable model to analyze the EMT‐MET dynamics that could affect development of triple negative breast cancer.