Epithelial-type systemic breast carcinoma cells with a restricted mesenchymal transition are a major source of metastasis

• DOI: 10.1126/sciadv.aav4275
• Publication Date: 2019-06-19T23:15:32Z
• Authors: Xiao Liu; Junjian Li; Bruno Loureiro Ca...; Anamarija Markota; Cornelia Voigt; Zhe Huang; Peter P. Lin; Daisy D. Wang; Juncheng Dai; Gisela Kranz; Anna Krandick; Darko Libl; Horst Zitzelsberger; Isabella Zagorski; Herbert Braselmann; Min Pan; Sibo Zhu; Yuanchi Huang; Sebastian Niederm...; Christoph A. Reichel; Bernd Uhl; Daria Briukhovetska; Javier Suárez; Sebastian Kobold; Olivier Gires; Hongxia Wang
• Keywords: Circulating tumor cell

Carcinoma cells undergo epithelial-mesenchymal transition (EMT); however, contributions of EMT heterogeneity to disease progression remain a matter debate. Here, we addressed the status ex vivo cultured circulating and disseminated tumor (CTCs/DTCs) in syngeneic mouse model metastatic breast cancer (MBC). Epithelial-type CTCs with restricted mesenchymal had strongest lung metastases formation ability, whereas mesenchymal-type showed limited ability. EpCAM expression served as surrogate marker evaluate clinical samples from MBC, including metastases, CTCs, DTCs. The proportion epithelial-type especially DTCs, correlated distant poorer outcome patients MBC. This study fosters our understanding metastasis underpins heterogeneous phenotypes important parameters for prognosis treatment. We further suggest that EpCAM-dependent CTC isolation systems will underestimate numbers but quantify clinically relevant cells.