Formation and regulation of the cancer stem cell niche.

It is widely accepted that tumors contain cancer stem cells (CSC) possessing self-renewal potential as well as the ability to generate numerous cancer cells. Cancer stem cells are resistant to conventional cancer therapy and have greater invasive and metastatic behavior. It has been suggested that blood vessels provide a niche that maintains stemness in normal organs. This role also extends to the field of cancer biology. Cancer stem cells have been isolated from leukemias and solid cancers. Identification of these cells and their niche is critical for identifying molecular targets in order to inhibit their growth and to destroy their niche. For this purpose, sorting of living CSC is required to monitor their presence in the presumptive niche to establish whether a CSC candidate actually shows malignant features. Based on and referring to analyses in normal tissues, molecules including nitric oxide, Wnt, neuropilin-1, hepatocyte growth factor and others involved in the maintenance of CSC have been isolated. Stem cells might affect niche cells and niche cells produce stemness factors on such stimulation. Therefore, the niche might be flexible to support self-renewal or differentiation of stem cells even in the same niche cells.