SDF-1 and PDGF enhance αvβ5-mediated ERK activation and adhesion-independent growth of human pre-B cell lines

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. Leukemia (2009) 23, 1807-1817; doi: 10.1038/leu.2009.126; published online 16 July 2009