Regulation of collagen-derived antiangiogenic factors by p53

Abstract

Background: Evidence suggests that the p53 tumor suppressor protein functions, in part, by limiting tumor angiogenesis. This effect is partly mediated by the ability of p53 to increase production of endogenous angiogenesis inhibitors, such as the collagen-derived antiangiogenic factors (CDAFs), endostatin and tumstatin. Objective: To review the clinical and therapeutic implications of CDAFs and their regulation by p53. Methods: We highlight the inhibitory role of CDAFs in angiogenesis and summarize evidence that p53 regulates the transcriptional program leading to their expression, synthesis, assembly and activation. Results/conclusion: The p53 gene is mutated in half of all human tumors and such cancers would be predicted to produce lower levels of CDAFs. We therefore believe that p53 function can be partially compensated by therapeutic use of CDAFs, which offers a promising new avenue for cancer treatment.

Keywords::

• angiogenic switch
• angiogenesis
• angiogenesis inhibitors
• antiangiogenic therapy
• collagen
• endostatin
• in situ tumors
• p53 tumor suppressor protein
• tumstatin