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

• Published in: Growth factors (Chur, Switzerland) Switzerland), 2010-10, Vol.28 (5), p.359-369
• Main Authors: Kricker, Jennifer A., Hyde, Carolyn E., Van Lonkhuyzen, Derek R., Hollier, Brett G., Shooter, Gary K., Leavesley, David I., Herington, Adrian C., Upton, Zee
• Format: Article
• Language: English
• Subjects: cell migration; heparin-binding; IGF-I; IGFBP; Vitronectin
• ISSN: 0897-7194; 1029-2292
• DOI: 10.3109/08977194.2010.494603

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.