Research Department: Cancer Biology
Graduation Date: May 2018
Abstract: Apoptosis, programmed cell death, is a highly conserved and tightly regulated process. Through efferocytosis, the engulfment of apoptotic cells, apoptosis culminates in the rapid and decisive removal of cell debris and local immune suppression. There are many ‘eat-me’ signals, yet the externalization of phosphatidylserine (PS) is the most well characterized signal that stimulates efferocytosis. PS is dysregulated in the tumor microenvironment and antagonizes the development of tumor immunity. Since tumor cells expose PS on their plasma membrane, we predict that tumor cells secrete increasing amounts of PS-expressing exosomes into the bloodstream that can be a biomarker for the early detection of cancer. We have developed a novel highly specific and sensitive enzyme-linked immunosorbent assay (ELISA) for the quantification of PS-positive exosomes for the early detection of cancer. Using a genetically engineered mouse model of pancreatic cancer, KrasLSL-G12D/+; Trp53LSL-R172h/+; PtflaCre/+ (KPC), we show the quantitative assessment of PS-positive exosomes detected at early stages of disease before clinical manifestations are observed. The data indicate that blood PS-exosome levels are a specific indicator for malignancies and suggest that assessment of PS-exosomes in blood is a biomarker for screening patients for early stage cancer.