Biology and clinical applications of pancreatic cancer stem cells.

Pancreatic ductal adenocarcinomas comprise a hierarchy of tumor cells that develop around a population of cancer stem cells. The cancer stem cells promote tumor growth and progression through a number of mechanisms, including differentiation into bulk tumor cells, metastasis, alteration of adjacent stromal cells, and evasion of conventional therapies. As with other cancer stem cells, pancreatic cancer stem cells (PCSCs) can be distinguished from bulk tumor cells based on their expression of unique surface markers, abilities to form spheres under nonadherent conditions and tumors in mice, and self-renewal and differentiation capacities. We review the markers used to identify PCSCs, the signaling pathways that regulate PCSC functions, the complex interactions between PCSCs and stromal cells, and approaches to therapeutically target PCSCs and improve treatment of patients with pancreatic cancer.