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Characterization of circulating breast cancer cells with tumorigenic and metastatic capacity

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Item Type:Article
Title:Characterization of circulating breast cancer cells with tumorigenic and metastatic capacity
Creators Name:Koch, C. and Kuske, A. and Joosse, S.A. and Yigit, G. and Sflomos, G. and Thaler, S. and Smit, D.J. and Werner, S. and Borgmann, K. and Gärtner, S. and Mossahebi Mohammadi, P. and Battista, L. and Cayrefourcq, L. and Altmüller, J. and Salinas-Riester, G. and Raithatha, K. and Zibat, A. and Goy, Y. and Ott, L. and Bartkowiak, K. and Tan, T.Z. and Zhou, Q. and Speicher, M.R. and Müller, V. and Gorges, T.M. and Jücker, M. and Thiery, J.P. and Brisken, C. and Riethdorf, S. and Alix-Panabières, C. and Pantel, K.
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.
Keywords:Breast Cancer, Circulating Tumor Cells, Functional Studies, Liquid Biopsy, Metastasis, Animals, Mice
Source:EMBO Molecular Medicine
Publisher:EMBO Press / Wiley
Page Range:e11908
Date:7 September 2020
Official Publication:https://doi.org/10.15252/emmm.201911908
PubMed:View item in PubMed

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