Post-transplant endothelial progenitor cell mobilization via CXCL10/CXCR3 signaling promotes liver tumor growth.

Autor: Ling CC; Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong, China., Ng KT; Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong, China., Shao Y; Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong, China., Geng W; Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong, China., Xiao JW; Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong, China., Liu H; Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong, China., Li CX; Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong, China., Liu XB; Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong, China., Ma YY; Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong, China., Yeung WH; Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong, China., Qi X; Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong, China., Yu J; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, China., Wong N; Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, China., Zhai Y; Department of Surgery, David Geffen School of Medicine, University of California at Los Angeles, USA., Chan SC; Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong, China., Poon RT; Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong, China; Center for Cancer Research, LKS Faculty of Medicine, The University of Hong Kong, China., Lo CM; Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong, China., Man K; Department of Surgery, LKS Faculty of Medicine, The University of Hong Kong, China; Center for Cancer Research, LKS Faculty of Medicine, The University of Hong Kong, China. Electronic address: kwanman@hkucc.hku.hk.
Jazyk: angličtina
Zdroj: Journal of hepatology [J Hepatol] 2014 Jan; Vol. 60 (1), pp. 103-9. Date of Electronic Publication: 2013 Aug 30.
DOI: 10.1016/j.jhep.2013.08.017
Abstrakt: Background & Aims: Patients with hepatocellular carcinoma (HCC) receiving living donor liver transplantation appear to possess significantly higher tumor recurrence than the recipients receiving deceased donor liver transplantation. The underlying mechanism for HCC recurrence after transplantation remains unclear. Here, we aim to investigate the impact of small-for-size liver graft injury on HCC recurrence after transplantation.
Methods: The correlation between tumor recurrence, liver graft injury, CXCL10 expression and endothelial progenitor cell (EPC) mobilization was studied in 115 liver transplant recipients and rat orthotopic liver transplantation (OLT) models. The direct role of CXCL10/CXCR3 signaling on EPC mobilization was investigated in CXCL10(-/-) mice and CXCR3(-/-) mice. The role of EPCs on tumor growth and angiogenesis was further investigated in an orthotopic liver tumor model.
Results: Clinically, patients with small-for-size liver grafts (<60% of standard liver weight, SLW) had significantly higher HCC recurrence (p=0.04), accompanied by more circulating EPCs and higher early-phase intragraft and plasma CXCL10 levels, than the recipients with large grafts (≥60% of SLW), which were further validated in rat OLT models. Circulatory EPC mobilization was reduced after liver injury both in CXCL10(-/-) mice and CXCR3(-/-) mice in comparison to wild-type controls. CXCL10 recruited EPCs in dose-dependent and CXCR3-dependent manners in vitro. Early-phase EPC/CXCL10 injection enhanced orthotopic liver tumor growth, angiogenesis and metastasis in nude mice.
Conclusions: Post-transplant enhanced CXCL10/CXCR3 signaling in small-for-size liver grafts directly induced EPC mobilization, differentiation and neovessel formation, which further promotes tumor growth. Targeting CXCL10/CXCR3 signaling may attenuate early-phase liver graft injury and prevent late-phase tumor recurrence/metastasis after transplantation.
(Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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