Interactions between osteopontin and vascular endothelial growth factor: Implications for cancer

For this comprehensive review, 257 publications with the keywords “osteopontin” or “OPN” and “vascular endothelial growth factor” or “VEGF” in PubMed were screened (time frame from year 1996 to year 2014). 37 articles were excluded because they were not focused on the interactions between these molecules, and papers relevant for transformation-related phenomena were selected. Osteopontin (OPN) and vascular endothelial growth factor (VEGF) are characterized by a convergence in function for regulating cell motility and angiogenesis, the response to hypoxia, and apoptosis. Often, they are co-expressed or one molecule induces the other, however, in some settings OPN-associated pathways and VEGF-associated pathways are distinct. Their relationships affect the pathogenesis in cancer, where they contribute to progression and angiogenesis and serve as markers for poor prognosis. The inhibition of OPN may reduce VEGF levels and suppress tumor progression. In vascular pathologies, these two cytokines mediate remodeling, but may also perpetuate inflammation and narrowing of the arteries. OPN and VEGF are elevated and contribute to vascularization in inflammatory diseases.