Mechanistic investigations into interactions between IGF-I and IGFBPs and their impact on facilitating cell migration on vitronectin

Abstract

Numerous studies have reported links between insulin-like growth factors (IGFs) and the extra-cellular matrix protein vitronectin (VN). We ourselves have reported that IGF-I binds to VN via IGF-binding proteins (IGFBPs) to stimulate HaCaT and MCF-7 cell migration. Here, we detail the functional evaluation of IGFBP-1, -2, -3, -4 and -6 in the presence and absence of IGF-I and VN. The data presented here, combined with our prior data on IGFBP-5, suggest that IGFBP-3, -4 and -5 are the most effective at stimulating cell migration in combination with IGF-I and VN. In addition, we demonstrate that different regions within IGFBP-3 and -4 are critical for complex formation. Furthermore, we examine whether multi-protein complexes of IGF-I and IGFBPs associated with fibronectin and collagen IV are also able to enhance functional biological responses.

Keywords::

• Vitronectin
• IGF-I
• IGFBP
• cell migration
• heparin-binding

Declaration of interest: This work was supported by the National Health and Medical Research Grant 290511, Australia, and the Tissue Repair and Regeneration Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, QLD, Australia. We would also like to acknowledge investigator stipends provided by the Dean's Doctoral Scholarship (J.A.K.) and Queensland Smart State Fellowship program (Z.U.). All authors have a duality of interest in terms of the fact that they hold shares or options in Tissue Therapies, a biotechnology start-up company that has been spun out of the Queensland University of Technology to commercialize this technology. The authors alone are responsible for the content and writing of the paper.