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Integrin-mediated action of insulin-like growth factor binding protein-2 in tumor cells

Title: Integrin-mediated action of insulin-like growth factor binding protein-2 in tumor cells
Authors: Schutt, BS; Langkamp, M; Rauschnabel, U; Ranke, MB; Elmlinger, MW
Source: Journal of Molecular Endocrinology ; volume 32, issue 3, page 859-868 ; ISSN 0952-5041 1479-6813
Publisher Information: Bioscientifica
Publication Year: 2004
Description: The neoplastic production of the insulin-like growth factor binding protein (IGFBP)-2 often correlates with tumor malignancy and aggressiveness. Since IGFBP-2 contains an RGD motif in its C-terminus, it was hypothesized that this protein may act independently of IGF on tumor cells through integrins. To investigate this, integrin binding, intracellular signaling and the impact of IGFBP-2 on cell adhesion and proliferation were examined in two tumor cell lines. In tracer displacement studies, up to 30% of the added (125)I-hIGFBP-2 specifically bound to the cells. Bound (125)I-hIGFBP-2 was reversibly displaced by IGFBP-2, IGFBP-1 and RGD-(Gly-Arg-Asp)-containing peptides, but not by IGFBP-3, -4, -5, -6 and RGE-(Gly-Arg-Glu)-containing peptides. Blocking with antibodies directed against different integrins and with fibronectin demonstrated that IGFBP-2 cell surface binding is specific for alpha5beta1-integrin. Incubation of IGFBP-2 with equimolar quantities of IGF-I and IGF-II annihilated RGD-specific binding. IGFBP-2 binding at the cell surface led to dephosphorylation of the focal adhesion-kinase (FAK) of up to 37% (P
Document Type: article in journal/newspaper
Language: unknown
DOI: 10.1677/jme.0.0320859
Availability: https://doi.org/10.1677/jme.0.0320859; https://jme.bioscientifica.com/view/journals/jme/32/3/859.xml; https://jme.bioscientifica.com/downloadpdf/journals/jme/32/3/859.xml
Accession Number: edsbas.69464EEF
Database: BASE