Characterization of circulating breast cancer cells with tumorigenic and metastatic capacity
Claudia Koch, Andra Kuske, Simon A. Joosse, Gökhan Yigit, George Sflomos, Sonja Thaler, Daniel J. Smit, Stefan Werner, Kerstin Borgmann, Sebastian Gärtner, Parinaz Mossahebi Mohammadi, Laura Battista, Laure Cayrefourcq, Janine Altmüller, Gabriela Salinas-Riester, Kaamini Raithatha, Arne Zibat, Y. Goy, Leonie Ott, Kai Bartkowiak, Tuan Zea Tan, Qing Zhou, Michael R. Speicher, Volkmar Müller, Tobias M. Gorges, Manfred Jücker, Jean Paul Thiery, Cathrin Brisken, Sabine Riethdorf, Catherine Alix‐Panabières, Klaus Pantel
Abstract
Abstract Functional studies giving insight into the biology of circulating tumor cells (CTCs) remain scarce due to the low frequency of CTCs and lack of appropriate models. Here, we describe the characterization of a novel CTC‐derived breast cancer cell line, designated CTC‐ITB‐01, established from a patient with metastatic estrogen receptor‐positive (ER + ) breast cancer, resistant to endocrine therapy. CTC‐ITB‐01 remained ER + in culture, and copy number alteration (CNA) profiling showed high concordance between CTC‐ITB‐01 and CTCs originally present in the patient with cancer at the time point of blood draw. RNA‐sequencing data indicate that CTC‐ITB‐01 has a predominantly epithelial expression signature. Primary tumor and metastasis formation in an intraductal PDX mouse model mirrored the clinical progression of ER + breast cancer. Downstream ER signaling was constitutively active in CTC‐ITB‐01 independent of ligand availability, and the CDK4/6 inhibitor Palbociclib strongly inhibited CTC‐ITB‐01 growth. Thus, we established a functional model that opens a new avenue to study CTC biology.