(667f) Identifying Secreted Biomarkers for Immune Evasion in Cellular Models of Cancer

Clinical management of cancer has been revolutionized following the introduction of molecular targeted therapies that promise both specificity and efficacy in treatment. Despite the initial clinical success of these drugs, the emergence of resistance is an increasing, and poorly understood problem. Acquired and de novo resistance to molecular targeted therapy is the manifestation of a complicated biochemical dialogue between the immune system, host microenvironment, and tumor cells that scientists are just beginning to unravel. One potential approach is to characterize the secretome of cancer cells, which consists of proteins that are secreted, shed from the cell surface, and intracellular proteins released into the supernatant due to cell lysis, apoptosis and necrosis. These proteins may contribute to escape from immunosurveillance and end up in the bloodstream thereby serving as potential noninvasive biomarkers. The objective of this study was to identify secreted proteins from two cellular models of breast cancer that may interfere with the immune response of the host. The secretome was collected from two cellular models of breast cancer, BT474 (HER2+/ER+) and SKBR3 (HER2+/ER-); separated using two dimensional electrophoresis (2DE); and identified using MALDI-TOF mass spectrometry. The proteins related to natural cell death, which have no contribution towards the breast cancer secretome, were subtracted from the sum of all proteins released by the cell culture. The impact of the identified proteins on immunosurveillance was characterized using pathway analysis and protein-network enrichment.