Article (Scientific journals)
Dual Roles for CXCL4 Chemokines and CXCR3 in Angiogenesis and Invasion of Pancreatic Cancer.
Quemener, Cathy; Baud, Jessica; Boye, Kevin et al.
2016In Cancer Research, 76 (22), p. 6507-6519
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Keywords :
CXCL4; chemokines; CXCR3; pancreatic cancer
Abstract :
[en] The CXCL4 paralog CXCL4L1 is a less studied chemokine that has been suggested to exert an antiangiogenic function. However, CXCL4L1 is also expressed in patient tumors, tumor cell lines, and murine xenografts, prompting a more detailed analysis of its role in cancer pathogenesis. We used genetic and antibody-based approaches to attenuate CXCL4L1 in models of pancreatic ductal adenocarcinoma (PDAC). Mechanisms of expression were assessed in cell coculture experiments, murine, and avian xenotransplants, including through an evaluation of CpG methylation and mutation of critical CpG residues. CXCL4L1 gene expression was increased greatly in primary and metastatic PDAC. We found that myofibroblasts triggered cues in the tumor microenvironment, which led to induction of CXCL4L1 in tumor cells. CXCL4L1 expression was also controlled by epigenetic modifications at critical CpG islands, which were mapped. CXCL4L1 inhibited angiogenesis but also affected tumor development more directly, depending on the tumor cell type. In vivo administration of an mAb against CXCL4L1 demonstrated a blockade in the growth of tumors positive for CXCR3, a critical receptor for CXCL4 ligands. Our findings define a protumorigenic role in PDAC development for endogenous CXCL4L1, which is independent of its antiangiogenic function. Cancer Res; 76(22); 6507-19. (c)2016 AACR.
Disciplines :
Biochemistry, biophysics & molecular biology
Oncology
Author, co-author :
Quemener, Cathy
Baud, Jessica
Boye, Kevin
Dubrac, Alexandre
Billottet, Clotilde
Soulet, Fabienne
Darlot, Florence
Dumartin, Laurent
Sire, Marie
Grepin, Renaud
Daubon, Thomas
Rayne, Fabienne
Wodrich, Harald
Couvelard, Anne
Pineau, Raphael
Schilling, Martin
Castronovo, Vincenzo ;  Université de Liège > Département des sciences biomédicales et précliniques > Biologie générale et cellulaire
Sue, Shih-Che
Clarke, Kim
Lomri, Abderrahim
Khatib, Abdel-Majid
Hagedorn, Martin
Prats, Herve
Bikfalvi, Andreas
More authors (14 more) Less
Language :
English
Title :
Dual Roles for CXCL4 Chemokines and CXCR3 in Angiogenesis and Invasion of Pancreatic Cancer.
Publication date :
2016
Journal title :
Cancer Research
ISSN :
0008-5472
eISSN :
1538-7445
Publisher :
American Association for Cancer Research, United States - Maryland
Volume :
76
Issue :
22
Pages :
6507-6519
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
(c)2016 American Association for Cancer Research.
Available on ORBi :
since 03 March 2017

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