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Immunology

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

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Abstract

CD23 acts through the αvβ5 integrin to promote growth of human pre-B cell lines in an adhesion-independent manner. αvβ5 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 αvβ5 and anti-αvβ5 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 αvβ5 with anti-αvβ5 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 αvβ5-mediated cell growth and ERK activation. The data suggest that adhesion-independent growth-promoting signals delivered to B-cell precursors through the αvβ5 integrin can be modulated by cross-talk with receptors linked to both G-protein and tyrosine kinase-coupled signalling pathways.

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Acknowledgements

MA and ALE were postgraduate scholars supported by the Wellcome Trust four-year PhD programme, Molecular Functions in Disease. BWO is supported by Cancer Research UK.

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Author notes

  1. M Acharya

    Present address: 3Current Address: Department of Pediatrics, Developmental Immunology Laboratory, Massachusetts General Hospital, Boston MA 02114, USA.,

  2. A L Edkins

    Present address: 4Current address: Chaperone Research Group, Department of Biochemistry, Microbiology and Biotechnology, Rhodes University, Grahamstown 6139, South Africa.,

Authors and Affiliations

  1. Division of Molecular and Cellular Biology, Faculty of Biomedical and Life Sciences, University of Glasgow, Glasgow, Scotland, UK

    M Acharya, A L Edkins & W Cushley

  2. Cancer Research-UK Beatson Laboratories, Garscube Estate, Glasgow, Scotland, UK

    B W Ozanne

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  1. M Acharya
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Correspondence to W Cushley.

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Acharya, M., Edkins, A., Ozanne, B. et al. SDF-1 and PDGF enhance αvβ5-mediated ERK activation and adhesion-independent growth of human pre-B cell lines. Leukemia 23, 1807–1817 (2009). https://doi.org/10.1038/leu.2009.126

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