The Insulin-like Growth Factor Binding Proteins (IGFBP1-6) mediate the biological activities of IGF proteins. IGF-I and IGF-II induce proliferation, migration, and differentiation of a wide variety of cell types including endothelial cells, vascular smooth muscle cells, and cancer cells. The effects of IGFBPs on angiogenesis and tumorigenesis are now being investigated.
Another molecule that may also regulate angiogenesis is Heme Oxygenase 1 (HO-1), an enzyme that is induced during hypoxia and inflammation. Its involvement in angiogenesis was suggested by the findings that HO-1 promotes endothelial cell proliferation in vitro, and HO-1 antagonists can inhibit VEGF-induced endothelial cell activities. Many studies indicate that HO-1 has a protective function in damaged vascular tissue by promoting endothelial progenitor cell mobilization and non-inflammatory VEGF-induced angiogenesis. While HO-1 may have beneficial effects for cardiovascular diseases, it is also frequently upregulated in tumors and is associated with tumor progression.
Somatostatin has been characterized as an anti-angiogenic molecule. It binds to one of five G protein-coupled Somatostain receptors (SSTR1-5) and has both anti-proliferative and anti-secretory effects.
Somatostatin receptors are expressed on both normal and cancer cells in multiple organs. Their activation has been shown to inhibit hormone secretion and to promote cell cycle arrest or apoptosis. In addition, SSTRs mediate the release of cytokines and growth factors such as IGF-I, FGF basic, and VEGF, inhibit monocyte chemotaxis, and prevent tumor cell proliferation. Determining the molecular mechanisms by which somatostatin functions is currently under investigation.