title: Osteoprotegerin regulates cancer cell migration through SDF-1/CXCR4 axis and promotes tumour development by increasing neovascularization.
abstract: We previously reported that OPG is involved in ischemic tissue neovascularization through the secretion of SDF-1 by pretreated-OPG endothelial colony-forming cells (ECFCs). As the vascularization is one of the key factor influencing the tumour growth and cancer cell dissemination, we investigated whether OPG was able to modulate the invasion of human MNNG-HOS osteosarcoma and DU145 prostate cancer cell lines in vitro and in vivo. Cell motility was analysed in vitro by using Boyden chambers. Human GFP-labelled MMNG-HOS cells were inoculated in immunodeficient mice and the tumour nodules formed were then injected with OPG and/or FGF-2, AMD3100 or 0.9% NaCl (control group). Tumour growth was manually followed and angiogenesis was assessed by immunohistochemistry. In vitro, SDF-1 released by OPG-pretreated ECFCs markedly attracted both MNNG-HOS and DU145 cells and induced spontaneous migration of cancer cells. In vivo, tumour volumes were significantly increased in OPG-treated group compared to the control group and OPG potentiated the effect of FGF-2. Concomitantly, OPG alone or combined with FGF-2 increased the number of new vasculature compared to the control group. Interestingly AMD3100, an inhibitor of SDF-1, prevented the in vivo effects of OPG induced by SDF-1 This study provides experimental evidence that OPG promotes tumour development trough SDF-1/CXCR4 axis.
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Paris, France; INSERM, UMR-S1140, Paris, France.
authors.forename: Zahia
authors.initials: Z
authors.lastname: Benslimane-Ahmim
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Paris, France; INSERM, UMR-S1140, Paris, France.
authors.forename: Jessica
authors.initials: J
authors.lastname: Pereira
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Paris, France; INSERM, UMR-S1140, Paris, France.
authors.forename: Anna
authors.initials: A
authors.lastname: Lokajczyk
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Paris, France; INSERM, UMR-S1140, Paris, France.
authors.forename: Blandine
authors.initials: B
authors.lastname: Dizier
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Paris, France; INSERM, UMR-S1140, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Galy-Fauroux
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Paris, France; INSERM, UMR-S1140, Paris, France; AP-HP, Haematology Department, Hôpital European Georges Pompidou, Paris, France.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Fischer
authors.affiliation: INSERM, European Associated Laboratory "Sarcoma Research Unit", Department of Oncology and Metabolism, University of Sheffield, Medical School, Beech Hill Road, S10 2RX, Sheffield, UK; INSERM, UMR 957, Pathophysiology of Bone Resorption and Therapy of Primary Bone Tumours, Equipe Ligue Contre le Cancer 2012, University of Nantes, Faculty of Medicine, 44035, Nantes, France; Nantes University Hospital, Nantes, 44035, France. Electronic address: dominique.heymann@sheffield.ac.uk.
authors.forename: Dominique
authors.initials: D
authors.lastname: Heymann
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Paris, France; INSERM, UMR-S1140, Paris, France. Electronic address: catherine.boisson-vidal@parisdescartes.fr.
authors.forename: Catherine
authors.initials: C
authors.lastname: Boisson-Vidal
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D054377:Chemokine CXCL12 / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000098:blood supply / Q000209:etiology* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000139:chemically induced*; D053244:Osteoprotegerin / Q000494:pharmacology*; D019718:Receptors, CXCR4 / Q000502:physiology*; D023041:Xenograft Model Antitumor Assays
chemical_list: C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D053244:Osteoprotegerin; D019718:Receptors, CXCR4; D016222:Fibroblast Growth Factor 2
keywords: Carcinoma; Osteoprotegerin; Osteosarcoma; SDF-1; Tumour angiogenesis