Stem cells in normal development and cancer.

In this chapter we provide an overview of stem cells in normal tissues as well as in many different types of cancers. All tissues in the body are derived from organ-specific stem cells that retain the ability to self-renew and differentiate into specific cell types. The cancer stem cell hypothesis suggests that tumors arise from cell populations with dysregulated self-renewal. This may be tissue stem cells or more differentiated cells that acquire self-renewal capabilities. In addition, we outline some useful assays for purification and isolation of cancer stem cells including the dye exclusion side population assay, flow cytometry sorting techniques for identification of putative cancer stem cell markers, tumorspheres assay, aldehyde dehydrogenase activity assay, PKH, and other membrane staining used to label the cancer stem cells, as well as in vivo xenograft transplantation assays. We also examine some of the cell signaling pathways that regulate stem cell self-renewal including the Notch, Hedgehog, HER2/PI3K/Akt/PTEN, and p53 pathways. We also review information demonstrating the involvement of the microenvironment or stem cell niche and its effects on the growth and maintenance of cancer stem cells. Finally, we highlight the therapeutic implications of targeting stem cells by inhibiting these pathways for the treatment and prevention of cancer.