Tumor Vasculature Is Regulated by FGF/FGFR Signaling-Mediated Angiogenesis and Bone Marrow-Derived Cell Recruitment: This Mechanism Is Inhibited by SSR128129E, the First Allosteric Antagonist of FGFRs

Autor: Françoise Bono, Jean-Marc Herbert, Dol Frédérique, Cécile Volle-Challier, Geneviève Gueguen-Dorbes, Paul J. Schaeffer, Fabien Geronimi, Joël Tuyaret, Jean-Pascal Herault, Pierre Fons
Rok vydání: 2014
Předmět:
Zdroj: Journal of Cellular Physiology. 230:43-51
ISSN: 0021-9541
DOI: 10.1002/jcp.24656
Popis: Tumor angiogenesis is accompanied by vasculogenesis, which is involved in the differentiation and mobilization of human bone marrow cells. In order to further characterize the role of vasculogenesis in the tumor growth process, the effects of FGF2 on the differentiation of human bone marrow AC133+ cells (BM-AC133+) into vascular precursors were studied in vitro. FGF2, like VEGFA, induced progenitor cell differentiation into cell types with endothelial cell characteristics. SSR128129E, a newly discovered specific FGFR antagonist acting by allosteric interaction with FGFR, abrogated FGF2-induced endothelial cell differentiation, showing that FGFR signaling is essential during this process. To assess the involvement of the FGF/FRGR signaling in vivo, the pre-clinical model of Lewis lung carcinoma (LL2) in mice was used. Subcutaneous injection of LL2 cells into mice induced an increase of circulating EPCs from peripheral blood associated with tumor growth and an increase of intra-tumoral vascular index. Treatment with the FGFR antagonist SSR128129E strongly decreased LL2 tumor growth as well as the intra-tumoral vascular index (41% and 50% decrease vs. vehicle-treated mice respectively, P
Databáze: OpenAIRE
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