α4β1 integrin associates with VEGFR2 in CLL cells and contributes to VEGF binding and intracellular signaling

5 p.-2 fig.In chronic lymphocytic leukemia (CLL), α4β1 integrin (the main α4 heterodimer in CLL) and vascular endothelial growth factor (VEGF) share several pathological properties, including involvement in cell migration and survival.Accordingly, elevated expression of α4 integrin (≥30% cells) constitutes an adverse prognostic marker and VEGF serum levels increase with CLL progression and could also have prognostic value. CLL cells express VEGF receptor 1 (VEGFR1), VEGFR2, and VEGFR3 receptors.VEGFR2 is the main signaling receptor in response to VEGF165 and its elevated expression correlates with CLL aggressivenes. Previous studies in endothelial cells have demonstrated interactions and functional cross talk between integrins (αvβ3, α9β1, α3β1, α5β1) and the VEGF/VEGFR2 system, including integrin-mediated adhesion to VEGF and VEGF-induced integrin activation.Moreover, shedding of syndecan-1 in endothelial cells induced coupling of α4β1 integrin and VEGFR2, VEGFR2 activation, and angiogenesis. It is not known whether α4β1 interacts with VEGF/VEGFR2 or/and contributes to VEGF functions in CLL and we have addressed this in the present study.This work was supported by grants SAF2015-69180R from the Ministry of Economy and Competitivity (Spain) and S2010/BMD-2314 from the Comunidad de Madrid/European Union (A.G.-P.).Peer reviewe