Characterization of circulating breast cancer cells with tumorigenic and metastatic capacity.
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Date
2020-09-07ICR Author
Author
Koch, C
Kuske, A
Joosse, SA
Yigit, G
Sflomos, G
Thaler, S
Smit, DJ
Werner, S
Borgmann, K
Gärtner, S
Mossahebi Mohammadi, P
Battista, L
Cayrefourcq, L
Altmüller, J
Salinas-Riester, G
Raithatha, K
Zibat, A
Goy, Y
Ott, L
Bartkowiak, K
Tan, TZ
Zhou, Q
Speicher, MR
Müller, V
Gorges, TM
Jücker, M
Thiery, J-P
Brisken, C
Riethdorf, S
Alix-Panabières, C
Pantel, K
Type
Journal Article
Metadata
Show full item recordAbstract
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.
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Research team
Endocrine control mechanisms
Language
eng
Date accepted
2020-06-17
License start date
2020-09
Citation
EMBO molecular medicine, 2020, 12 (9), pp. e11908 - ?
Publisher
WILEY