Cancer stem cells and angiogenesis.

Most cancers contain tumor cells that display stem cell-like characteristics. How and when such cells appear in tumors are not clear, but may involve both stochastic as well as hierarchical events. Most likely, tumor cells that display stem cell-like characteristics can undergo asymmetric cell division giving rise to tumor cells that trigger angiogenic programs. As normal stem cells the cancer stem-like cells seem to adapt to hypoxic environments and will use metabolic pathways that involve increased conversion of glucose to pyruvate and lactate, and a concomitant decrease in mitochondrial metabolism and mitochondrial mass. The molecular pathways responsible for inducing glycolysis are now being explored. These pathways seem to mediate multiple metabolic functions in cancer stem-like cells, leading to a highly migratory and angiogenesis-independent phenotype. Future challenges will be to identify and validate molecular targets involved in anaerobic metabolic pathways active in cancer stem-like cells and to determine how these pathways differ from regulatory pathways involved in normal stem cell function.