Methods of producing growth factor complex
An isolated protein complex is provided which includes a growth factor, growth factor binding protein and vitronectin. Preferably, the isolated protein complex includes an insulin-like growth factor-I, insulin-like growth factor binding protein-3 or insulin-like growth factor binding protein-5 and vitronectin. Also provided are methods of modulating cell proliferation and/or migration by administering said protein complex for the purposes of wound healing, skin repair and tissue replacement therapy. Conversely, by using agents that disrupt growth factor protein complexes formed in vivo, growth factor-driven cell proliferation and/or migration may be suppressed such as for the purposes of treating cancers, psoriasis, atherosclerosis and wounds prone to hypertrophic scarring.
1. A method of producing an isolated protein complex consisting of an insulin like growth factor (IGF-I), an insulin like growth factor binding protein (IGFBP) and vitronectin, said method including the sequential steps of binding said IGFBP to vitronectin and binding IGF-I- to said IGFBP.
2. A method of producing an isolated protein complex consisting of an IGF-I, an insulin like growth factoring binding protein (IGFBP) and vitronectin, said method including the step of binding said IGFBP with IGF-I bound thereto, to vitronectin.
3. The method of claim 1 , wherein the IGFBP is IGFBP3 or IGFBP5.
4. The method of claim 3 , wherein the IGFBP is IGFBP3.
5. The method of claim 1 , wherein vitronectin is monomeric.
6. The method of claim 1 , wherein vitronectin is multimeric.
7. The method of claim 1 , wherein vitronectin is bound or immobilized to a substrate.
8. An isolated protein complex consisting of IGF-I, an insulin like growth factor binding protein (IGFBP) and vitronectin, produced according to the method of claim 1 .
9. A surgical implant or prosthesis comprising the isolated protein complex of claim 8 .