title: Control of both myeloid cell infiltration and angiogenesis by CCR1 promotes liver cancer metastasis development in mice.
abstract: Expression of the CC chemokine receptor 1 (CCR1) by tumor cells has been associated with protumoral activity; however, its role in nontumoral cells during tumor development remains elusive. Here, we investigated the role of CCR1 deletion on stromal and hematopoietic cells in a liver metastasis tumor model. Metastasis development was strongly impaired in CCR1-deficient mice compared to control mice and was associated with reduced liver monocyte infiltration. To decipher the role of myeloid cells, sublethally irradiated mice were reconstituted with CCR1-deficient bone marrow (BM) and showed better survival rates than the control reconstituted mice. These results point toward the involvement of CCR1 myeloid cell infiltration in the promotion of tumor burden. In addition, survival rates were extended in CCR1-deficient mice receiving either control or CCR1-deficient BM, indicating that host CCR1 expression on nonhematopoietic cells also supports tumor growth. Finally, we found defective tumor-induced neoangiogenesis (in vitro and in vivo) in CCR1-deficient mice. Overall, our results indicate that CCR1 expression by both hematopoietic and nonhematopoietic cells favors tumor aggressiveness. We propose CCR1 as a potential therapeutical target for liver metastasis therapy.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, INSERM UMR-S 945-IUC, Paris, France.
authors.forename: Mathieu Paul
authors.initials: MP
authors.lastname: Rodero
authors.forename: Constance
authors.initials: C
authors.lastname: Auvynet
authors.forename: Lucie
authors.initials: L
authors.lastname: Poupel
authors.forename: Behazine
authors.initials: B
authors.lastname: Combadière
authors.forename: Christophe
authors.initials: C
authors.lastname: Combadière
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D005260:Female; D008099:Liver / Q000098:blood supply* / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology* / Q000556:secondary* / Q000628:therapy; D008114:Liver Neoplasms, Experimental / Q000235:genetics / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009000:Monocytes / Q000473:pathology; D022423:Myeloid Cells / Q000473:pathology*; D009389:Neovascularization, Pathologic; D054389:Receptors, CCR1 / Q000235:genetics / Q000378:metabolism*; D015996:Survival Rate
chemical_list: C515301:Ccr1 protein, mouse; D054389:Receptors, CCR1