CXCR7 contributes to the aggressive phenotype of cholangiocarcinoma cells

Alessandra Gentilini¹, Alessandra Caligiuri², Chiara Raggi³, Krista Rombouts⁴, Massimo Pinzani⁵, Giulia Lori⁶, Margherita Correnti⁷, Pietro Invernizzi⁸, Elisabetta Rovida⁹, Nadia Navari¹⁰, Sabina Di Matteo¹¹, Domenico Alvaro¹², Jesus M Banales¹³, Pedro Rodrigues¹⁴, Carlotta Raschioni¹⁵, Matteo Donadon¹⁶, Luca Di Tommaso¹⁷, Fabio Marra¹⁸

Affiliations

¹ Department of Experimental and Clinical Medicine, University of Florence, Italy. Electronic address: [email protected].
² Department of Experimental and Clinical Medicine, University of Florence, Italy. Electronic address: [email protected].
³ Department of Experimental and Clinical Medicine, University of Florence, Italy; Center for Autoimmune Liver Diseases IRCCS Istituto Clinico Humanitas, Rozzano, MI, Italy. Electronic address: [email protected].
⁴ University College London (UCL), Institute for Liver and Digestive Health, Royal Free Hospital, London, UK. Electronic address: [email protected].
⁵ University College London (UCL), Institute for Liver and Digestive Health, Royal Free Hospital, London, UK. Electronic address: [email protected].
⁶ Department of Experimental and Clinical Medicine, University of Florence, Italy. Electronic address: [email protected].
⁷ Center for Autoimmune Liver Diseases IRCCS Istituto Clinico Humanitas, Rozzano, MI, Italy. Electronic address: [email protected].
⁸ University of Milan Bicocca, Milan, Italy. Electronic address: [email protected].
⁹ Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Italy. Electronic address: [email protected].
¹⁰ Department of Experimental and Clinical Medicine, University of Florence, Italy. Electronic address: [email protected].
¹¹ Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy. Electronic address: [email protected].
¹² Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy. Electronic address: [email protected].
¹³ Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, CIBERehd, Ikerbasque, San Sebastian, Spain. Electronic address: [email protected].
¹⁴ Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, CIBERehd, Ikerbasque, San Sebastian, Spain. Electronic address: [email protected].
¹⁵ Oncology Experimental Therapeutics, Humanitas Clinical and Research Center, Rozzano, Milan, Italy. Electronic address: [email protected].
¹⁶ Department of Pathology, IRCCS Humanitas Clinical Institute, Rozzano, MI, Italy. Electronic address: [email protected].
¹⁷ Pathology Unit, Humanitas Clinical and Research Center, Rozzano, MI, Italy; Department of Biomedical Sciences, Humanitas University, Rozzano, MI, Italy. Electronic address: [email protected].
¹⁸ Department of Experimental and Clinical Medicine, University of Florence, Italy. Electronic address: [email protected].

PMID: 31059778
DOI: 10.1016/j.bbadis.2019.04.020

Free article

CXCR7 contributes to the aggressive phenotype of cholangiocarcinoma cells

Alessandra Gentilini et al. Biochim Biophys Acta Mol Basis Dis. 2019.

Free article

. 2019 Sep 1;1865(9):2246-2256.

doi: 10.1016/j.bbadis.2019.04.020. Epub 2019 May 3.

Authors

Affiliations

¹ Department of Experimental and Clinical Medicine, University of Florence, Italy. Electronic address: [email protected].
² Department of Experimental and Clinical Medicine, University of Florence, Italy. Electronic address: [email protected].
³ Department of Experimental and Clinical Medicine, University of Florence, Italy; Center for Autoimmune Liver Diseases IRCCS Istituto Clinico Humanitas, Rozzano, MI, Italy. Electronic address: [email protected].
⁴ University College London (UCL), Institute for Liver and Digestive Health, Royal Free Hospital, London, UK. Electronic address: [email protected].
⁵ University College London (UCL), Institute for Liver and Digestive Health, Royal Free Hospital, London, UK. Electronic address: [email protected].
⁶ Department of Experimental and Clinical Medicine, University of Florence, Italy. Electronic address: [email protected].
⁷ Center for Autoimmune Liver Diseases IRCCS Istituto Clinico Humanitas, Rozzano, MI, Italy. Electronic address: [email protected].
⁸ University of Milan Bicocca, Milan, Italy. Electronic address: [email protected].
⁹ Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Italy. Electronic address: [email protected].
¹⁰ Department of Experimental and Clinical Medicine, University of Florence, Italy. Electronic address: [email protected].
¹¹ Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy. Electronic address: [email protected].
¹² Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy. Electronic address: [email protected].
¹³ Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, CIBERehd, Ikerbasque, San Sebastian, Spain. Electronic address: [email protected].
¹⁴ Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, CIBERehd, Ikerbasque, San Sebastian, Spain. Electronic address: [email protected].
¹⁵ Oncology Experimental Therapeutics, Humanitas Clinical and Research Center, Rozzano, Milan, Italy. Electronic address: [email protected].
¹⁶ Department of Pathology, IRCCS Humanitas Clinical Institute, Rozzano, MI, Italy. Electronic address: [email protected].
¹⁷ Pathology Unit, Humanitas Clinical and Research Center, Rozzano, MI, Italy; Department of Biomedical Sciences, Humanitas University, Rozzano, MI, Italy. Electronic address: [email protected].
¹⁸ Department of Experimental and Clinical Medicine, University of Florence, Italy. Electronic address: [email protected].

PMID: 31059778
DOI: 10.1016/j.bbadis.2019.04.020

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.

Keywords: Cancer stem cells; Cell migration; Chemokines; Liver stromal cells; β-Arrestin 2.

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CXCR7 contributes to the aggressive phenotype of cholangiocarcinoma cells

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CXCR7 contributes to the aggressive phenotype of cholangiocarcinoma cells

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Abstract

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Medical