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CXCR7 contributes to the aggressive phenotype of cholangiocarcinoma cells

Gentilini, A; Caligiuri, A; Raggi, C; Rombouts, K; Pinzani, M; Lori, G; Correnti, M; ... Marra, F; + view all (2019) CXCR7 contributes to the aggressive phenotype of cholangiocarcinoma cells. Biochimica et Biophysica Acta (BBA): Molecular Basis of Disease , 1865 (9) pp. 2246-2256. 10.1016/j.bbadis.2019.04.020. Green open access

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Abstract

Development of cholangiocarcinoma (CCA) is dependent on a cross-talk with stromal cells, which release different chemokines including CXCL12, that interacts with two different receptors, CXCR4 and CXCR7. The aim of the present study was to investigate the role of CXCR7 in CCA cells. CXCR7 is overexpressed by different CCA cell lines and in human CCA specimens. Knock-down of CXCR7 in HuCCT-1 cells reduced migration, invasion, and CXCL12-induced adhesion to collagen I. Survival of CCA was also reduced in CXCR7-silenced cells. The ability of CXCL12 to induce cell migration and survival was also blocked by CCX733, a CXCR7 antagonist. Similar effects of CXCR7 activation were observed in CCLP-1 cells and in primary iCCA cells. Enrichment of tumor stem-like cells by a 3D culture system resulted in increased CXCR7 expression compared to cells grown in monolayers, and genetic knockdown of CXCR7 robustly reduced sphere formation both in HuCCT-1 and in CCLP-1 cells. In HuCCT-1 cells CXCR7 was found to interact with β-arrestin 2, which was necessary to mediate CXCL12-induced migration, but not survival. In conclusion, CXCR7 is widely expressed in CCA, and contributes to the aggressive phenotype of CCA cells, inducing cell migration, invasion, adhesion, survival, growth and stem cell-like features. Cell migration induced by CXCR7 requires interaction with β-arrestin 2.

Type: Article
Title: CXCR7 contributes to the aggressive phenotype of cholangiocarcinoma cells
Location: Netherlands
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.bbadis.2019.04.020
Publisher version: https://doi.org/10.1016/j.bbadis.2019.04.020
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Cancer stem cells, Cell migration, Chemokines, Liver stromal cells, β-Arrestin 2
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inst for Liver and Digestive Hlth
URI: https://discovery.ucl.ac.uk/id/eprint/10074497
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