SDF-1 and PDGF enhance [alpha]v[beta]5-mediated ERK activation and adhesion-independent growth of human pre-B cell lines

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Acharya, M. ; Edkins, A.L. ; Ozanne, B.W. ; Cushley, W. (2009)

CD23 acts through the [alpha]v[beta]5 integrin to promote growth of human pre-B cell lines in an adhesion-independent manner. [alpha]v[beta]5 is expressed on normal B-cell precursors in the bone marrow. Soluble CD23 (sCD23), short CD23-derived peptides containing the arg-lys-cys (RKC) motif recognized by [alpha]v[beta]5 and anti-[alpha]v[beta]5 monoclonal antibodies (MAbs) all sustain growth of pre-B cell lines. The chemokine stromal cell-derived factor-1 (SDF-1) regulates key processes during B-cell development. SDF-1 enhanced the growth-sustaining effect driven by ligation of [alpha]v[beta]5 with anti-[alpha]v[beta]5 MAb 15F-11, sCD23 or CD23-derived RKC-containing peptides. This effect was restricted to B-cell precursors and was specific to SDF-1. The enhancement in growth was associated with the activation of extracellular signal-regulated kinase (ERK) and both these responses were attenuated by the MEK inhibitor U0126. Finally, platelet-derived growth factor also enhanced both [alpha]v[beta]5-mediated cell growth and ERK activation. The data suggest that adhesion-independent growth-promoting signals delivered to B-cell precursors through the [alpha]v[beta]5 integrin can be modulated by cross-talk with receptors linked to both G-protein and tyrosine kinase-coupled signalling pathways.
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