Human defensins as cancer biomarkers and antitumour molecules

Abstract

Human defensins, which are small cationic peptides produced by neutrophils and epithelial cells, form two genetically distinct alpha and beta subfamilies. They are involved in innate immunity through killing microbial pathogens or neutralizing bacterial toxins and in adaptive immunity by serving as chemoattractants and activators of immune cells. alpha-defensins are mainly packaged in neutrophil granules (HNP1, HNP2, HNP3) or secreted by intestinal Paneth cells (HD5, HD6), while beta-defensins are expressed in mucosa and epithelial cells. Using surface enhanced laser desorption/ionisation time-of-flight (SELDI-TOF) mass spectrometry (MS), alpha-defensins were found to be expressed in a variety of human tumours, either in tumour cells or at their surface. HNP1-3 peptides are also secreted and their accumulation in biological fluids was proposed as a tumour biomarker. Conversely, beta-defensin-1 (HBD-1) is down-regulated in some tumour types in which it could behave as a tumour suppressor protein. Alpha-defensins promote tumour cell growth or, at higher concentration, provoke cell death. These peptides also inhibit angiogenesis, which, in addition to immunomodulation, indicates a complex role in tumour development. This review summarizes current knowledge of defensins to discuss their role in tumour growth, tumour monitoring and cancer treatment.