Synthetic chimeric proteins comprising epidermal growth factor and vitronectin

摘要

Isolated protein complexes are provided comprising growth factors such as IGF-I, IGF-II, EGF, bFGF, KGF, VEGF or PDGF, or at least domains thereof that enable binding to and activation of both a growth factor receptor, and an integrin receptor-binding domain of vitronectin or fibronectin. These protein complexes may be in the form of oligo-protein complexes or single, synthetic proteins where the growth factor and vitronectin or fibronectin sequences are joined by a linker sequence. In particular forms, vitronectin or fibronectin sequences do not include a heparin binding domain and/or polyanionic domain. Also provided are uses of these protein complexes for stimulating or inducing cell migration and/or proliferation which may have use in wound healing, tissue engineering, cosmetic and therapeutic treatments such as skin replacement and skin replenishment and treatment of burns where epithelial cell migration is required. In other embodiments, the invention provides inhibition of cancer cell metastasis, particularly in relation to breast cancer.

主权项

1. An isolated protein complex in the form of a synthetic chimeric protein, comprising an amino add sequence of:
(i) a growth factor selected from epidermal growth factor (EGF), basic fibroblast growth factor (bFGF) and keratinocyte growth factor (KGF), or at least a domain of said growth factor which is capable of binding a cognate growth factor receptor; and (ii) vitronectin (VN) or a fragment of VN comprising at least an integrin-binding domain, wherein said at least an integrin-binding domain comprises the sequence RGD and facilitates cell attachment.