PMID: 15375510Sep 18, 2004Paper

Synergistic induction of in vivo angiogenesis by the combination of insulin-like growth factor-II and epidermal growth factor

Oncology Reports
You Mie LeeKyu-Won Kim

Abstract

Tumor growth is accelerated by induction of angiogenesis regulated by many cytokines and growth factors. In a tumor mass, various angiogenic factors and their receptors are simultaneously expressed and the overlapped expressions of various factors may contribute to the aggressive growth of tumor. However, the possible combined effect and mechanism of growth factors involved in angiogenesis are still under investigated. Insulin-like growth factor-II (IGF-II) has been identified as an angiogenic factor and highly expressed in solid tumors. Here we demonstrated that another angiogenic factor, epidermal growth factor (EGF), synergistically induced the angiogenic activity when co-treated with IGF-II in vivo. We performed mouse Matrigel plug assay. Cotreatment of IGF-II and EGF resulted in a significant induction of functional new vessels in mouse Matrigel plug more than additive amount of vessels induced by each growth factor. However, synergism of these two factors was not found in in vitro angiogenic assays, i.e., in migration and proliferation assays. The metalloproteinase-2 (MMP-2) protein level was enhanced by co-treatment of IGF-II and EGF, similar to that of individual treatment of them or PMA or bFGF. EGF down-regulated hypo...Continue Reading

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