EMBO Molecular Medicine (Sep 2020)
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,
- Yvonne 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
Affiliations
- Claudia Koch
- Department of Tumor Biology Center of Experimental Medicine University Medical Center Hamburg‐Eppendorf Hamburg Germany
- Andra Kuske
- Department of Tumor Biology Center of Experimental Medicine University Medical Center Hamburg‐Eppendorf Hamburg Germany
- Simon A Joosse
- Department of Tumor Biology Center of Experimental Medicine University Medical Center Hamburg‐Eppendorf Hamburg Germany
- Gökhan Yigit
- Institute of Human Genetics University Medical Center Göttingen Göttingen Germany
- George Sflomos
- ISREC – Swiss Institute for Experimental Cancer Research School of Life Sciences Ecole Polytechnique Fédérale de Lausanne (EPFL) Lausanne Switzerland
- Sonja Thaler
- European Centre for Angioscience (ECAS) Medical Faculty Mannheim University of Heidelberg Mannheim Germany
- Daniel J Smit
- Institute of Biochemistry and Signal Transduction University Medical Center Hamburg‐Eppendorf Hamburg Germany
- Stefan Werner
- Department of Tumor Biology Center of Experimental Medicine University Medical Center Hamburg‐Eppendorf Hamburg Germany
- Kerstin Borgmann
- Radiobiology& Experimental Radiooncology University Medical Center Hamburg‐Eppendorf Hamburg Germany
- Sebastian Gärtner
- Department of Tumor Biology Center of Experimental Medicine University Medical Center Hamburg‐Eppendorf Hamburg Germany
- Parinaz Mossahebi Mohammadi
- Department of Tumor Biology Center of Experimental Medicine University Medical Center Hamburg‐Eppendorf Hamburg Germany
- Laura Battista
- ISREC – Swiss Institute for Experimental Cancer Research School of Life Sciences Ecole Polytechnique Fédérale de Lausanne (EPFL) Lausanne Switzerland
- Laure Cayrefourcq
- Laboratory of Rare Human Circulating Cells (LCCRH) University Medical Centre Montpellier France
- Janine Altmüller
- Cologne Center for Genomics University of Cologne Cologne Germany
- Gabriela Salinas‐Riester
- NGS Integrative Genomics Core Unit Institute of Human Genetics University Medical Center Göttingen Göttingen Germany
- Kaamini Raithatha
- NGS Integrative Genomics Core Unit Institute of Human Genetics University Medical Center Göttingen Göttingen Germany
- Arne Zibat
- Institute of Human Genetics University Medical Center Göttingen Göttingen Germany
- Yvonne Goy
- Radiobiology& Experimental Radiooncology University Medical Center Hamburg‐Eppendorf Hamburg Germany
- Leonie Ott
- Department of Tumor Biology Center of Experimental Medicine University Medical Center Hamburg‐Eppendorf Hamburg Germany
- Kai Bartkowiak
- Department of Tumor Biology Center of Experimental Medicine University Medical Center Hamburg‐Eppendorf Hamburg Germany
- Tuan Zea Tan
- Cancer Science Institute of Singapore National University of Singapore Singapore City Singapore
- Qing Zhou
- Institute of Human Genetics Diagnostic and Research Center for Molecular BioMedicine Medical University of Graz Graz Austria
- Michael R Speicher
- Institute of Human Genetics Diagnostic and Research Center for Molecular BioMedicine Medical University of Graz Graz Austria
- Volkmar Müller
- Department of Gynecology University Medical Center Hamburg‐Eppendorf Hamburg Germany
- Tobias M Gorges
- Department of Tumor Biology Center of Experimental Medicine University Medical Center Hamburg‐Eppendorf Hamburg Germany
- Manfred Jücker
- Institute of Biochemistry and Signal Transduction University Medical Center Hamburg‐Eppendorf Hamburg Germany
- Jean‐Paul Thiery
- INSERM Unit 1186 Comprehensive Cancer Center Institut Gustave Roussy Villejuif France
- Cathrin Brisken
- ISREC – Swiss Institute for Experimental Cancer Research School of Life Sciences Ecole Polytechnique Fédérale de Lausanne (EPFL) Lausanne Switzerland
- Sabine Riethdorf
- Department of Tumor Biology Center of Experimental Medicine University Medical Center Hamburg‐Eppendorf Hamburg Germany
- Catherine Alix‐Panabières
- Laboratory of Rare Human Circulating Cells (LCCRH) University Medical Centre Montpellier France
- Klaus Pantel
- Department of Tumor Biology Center of Experimental Medicine University Medical Center Hamburg‐Eppendorf Hamburg Germany
- DOI
- https://doi.org/10.15252/emmm.201911908
- Journal volume & issue
-
Vol. 12,
no. 9
pp. n/a – n/a
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.
Keywords