Method of treating a disease or condition characterized by aberrant epithelial cell proliferation
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 treating a disease or condition characterized by aberrant epithelial cell proliferation and/or migration, said method including the step of administering to a mammal an agent which disrupts an isolated protein complex comprising: insulin-like growth factor I (IGF-I); an insulin-like growth factor binding protein (IGFBP) selected from IGFBP-3 and IGFBP-5; and vitronectin; or which prevents formation of the isolated protein complex, to thereby treat said disease or condition in said mammal, wherein the agent is selected from the group consisting of IGF-II and IGF-II having a deletion or non-conservative substitution of one or more amino acid residues selected from: (i) V35; (ii) S36; and (iii) S39; of an RVSRRSR (SEQ ID NO:1) sequence at positions 34-40 in the C-domain of IGF-II.
2. The method of claim 1 , wherein the disease or condition characterized by aberrant epithelial cell proliferation and/or migration is a cancer.
3. The method of claim 2 , for inhibiting tumour metastasis.
4. The method of claim 2 , for inhibiting tumour growth.
5. The method of claim 1 , wherein the disease or condition is characterized by aberrant epithelial cell proliferation and/or migration is psoriasis.
6. The method of claim 1 , wherein the disease or condition characterized by aberrant epithelial cell proliferation and/or migration is epithelial breast cancer.
7. The method of claim 1 , wherein the agent is IGF-II.
8. The method of claim 1 , wherein the agent is IGF-II having a deletion or non-conservative substitution of or one or more amino acid residues selected from: (i) V 35 ; (ii) S 36 ; and (iii) S 39 ; of an RVSRRSR (SEQ ID NO:1) sequence at positions 34-40 in the C-domain of IGF-II.