Chimeric vitronectin:insulin-like growth factor proteins enhance cell growth and migration through co-activation of receptors.
Complexes comprised of IGF-I, IGF-binding proteins and the ECM protein vitronectin (VN) stimulate cell migration and growth and can replace the requirement for serum for the ex vivo expansion of cells, as well as promote wound healing in vivo. Moreover, the activity of the complexes is dependent on co-activation of the IGF-I receptor and VN-binding integrins. In view of this we sought to develop chimeric proteins able to recapitulate the action of the multiprotein complex within a single molecular species. We report here the production of two recombinant chimeric proteins, incorporating domains of VN linked to IGF-I, which mimic the functions of the complex. Further, the activity of the chimeric proteins is dependent on co-activation of the IGF-I- and VN-binding cell surface receptors. Clearly the use of chimeras that mimic the activity of growth factor:ECM complexes, such as these, offer manufacturing advantages that ultimately will facilitate translation to cost-effective therapies.
Van Lonkhuyzen
Derek R
DR
Tissue Repair and Regeneration Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Queensland, Australia. d.vanlonkhuyzen@qut.edu.au
Hollier
Brett G
BG
Shooter
Gary K
GK
Leavesley
David I
DI
Upton
Zee
Z
D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D054443:Cell Migration Assays; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis* / Q000378:metabolism; D039564:Integrin alphaV / Q000378:metabolism; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis* / Q000378:metabolism; D020539:Sequence Analysis, Protein; D015398:Signal Transduction / Q000502:physiology; D019096:Vitronectin / Q000096:biosynthesis* / Q000378:metabolism
D039564:Integrin alphaV; D011993:Recombinant Fusion Proteins; D019096:Vitronectin; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1