Insulin-like growth factors (IGF) and IGF-binding proteins bound to vitronectin enhance keratinocyte protein synthesis and migration

J Invest Dermatol. 2004 May;122(5):1198-206. doi: 10.1111/j.0022-202X.2004.22527.x.


The insulin-like growth factor (IGF) system plays an important role in a number of disease states, such as cancer and psoriasis, through its ability to modulate cell proliferation, attachment, and migration. The type-1 IGF and type-2 IGF receptors, as well as six IGF-binding proteins (IGFBP-1-6), have well-established roles in mediating IGF activity. Additionally, it's been demonstrated that IGF-II binds directly to the extracellular matrix protein vitronectin (VN), whereas IGF-I does not. IGFBP-5, however, has been recently demonstrated to facilitate the binding of IGF-I to VN. The aim of this study was to determine whether the interaction between IGF, IGFBP, and VN modulates human keratinocyte function. Functional assays demonstrated that both the IGF-II:VN and IGF-I:IGFBP-5:VN complexes resulted in significantly enhanced protein synthesis and cell migration through 12 microm pore Transwells in skin keratinocytes (HaCAT). Furthermore, the IGF-II:VN complex significantly enhanced human corneal epithelial (HCE) cell protein synthesis. Interestingly, the IGF-II:VN complex did not effect either HCE cell migration or attachment. This is the first study to demonstrate a functional role for the interaction between IGF and VN in human keratinocytes. Moreover, these results suggest that IGF-II:VN and IGF-I:IGFBP-5:VN complexes may be useful in situations where enhanced keratinocyte cell migration and proliferation is required, such as in wound healing and skin regeneration.

MeSH terms

  • Cell Adhesion / drug effects
  • Cell Adhesion / physiology
  • Cell Movement / drug effects
  • Cell Movement / physiology
  • Cells, Cultured
  • Dimerization
  • Humans
  • Insulin-Like Growth Factor Binding Protein 5 / chemistry
  • Insulin-Like Growth Factor Binding Protein 5 / metabolism*
  • Insulin-Like Growth Factor Binding Protein 5 / pharmacology
  • Insulin-Like Growth Factor I / chemistry
  • Insulin-Like Growth Factor I / metabolism*
  • Insulin-Like Growth Factor I / pharmacology
  • Insulin-Like Growth Factor II / chemistry
  • Insulin-Like Growth Factor II / metabolism*
  • Insulin-Like Growth Factor II / pharmacology
  • Keratinocytes / cytology
  • Keratinocytes / metabolism*
  • Protein Binding / physiology
  • Protein Biosynthesis
  • Vitronectin / chemistry
  • Vitronectin / metabolism*
  • Vitronectin / pharmacology
  • Wound Healing / physiology


  • Insulin-Like Growth Factor Binding Protein 5
  • Vitronectin
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor II