Circulating Exosomes in Pancreatic Cancer: Will They Succeed on the Long, Littered Road to Early Detection Marker?

摘要

Pancreatic cancer is the fourth leading cause of cancer death in the US and is projected to be the second leading cause of cancer death by 2020. The high mortality of pancreatic ductal adenocarcinoma (PDAC),3 the most common form of pancreatic cancer, is largely a consequence of diagnosis at an advanced stage, when the tumor can no longer be surgically resected for cure. Nevertheless, symptoms rarely develop with early disease, and established risk factors for PDAC—tobacco smoking, obesity, personal history of chronic pancreatitis or diabetes, and family history of pancreatic cancer—are insufficient to risk-stratify the population to facilitate disease screening. Despite extensive research efforts and many potential candidates, no noninvasive biomarker has reached the clinic with utility for early detection of PDAC.Experimental studies indicate that more than a decade elapses from formation of the founder malignant clone to a patient's diagnosis, suggesting a window of opportunity for early detection. With this issue in mind, 2 recent studies have exposed new and interesting biology related to the release of exosomes from pancreatic tumors into peripheral blood (1, 2), raising the possibility of a noninvasive tool for risk stratification and earlier PDAC diagnosis.Exosomes are small, extracellular membrane–enclosed vesicles released from most cell types. Because they initially form from intracellular compartments, they contain nucleic acids and proteins, which can be transferred to other cells upon fusion with their extracellular membrane. Although the full spectrum of exosome biology remains to be defined, it is increasingly clear that exosomes are secreted from cancer cells at higher rates than from healthy cells and are important in facilitating cancer progression and spread (3).By use of proteomics, Melo et al. (1) compared exosomes secreted from cancer cell lines and nontumorigenic cells and identified glypican 1 (GPC1) as a membrane-bound protein preferentially present …