The origin of the cancer stem cell: current controversies and new insights

Abstract

Most tumours are derived from a single cell that is transformed into a cancer-initiating cell (cancer stem cell) that has the capacity to proliferate and form tumours in vivo. However, the origin of the cancer stem cell remains elusive. Interestingly, during development and tissue repair the fusion of genetic and cytoplasmic material between cells of different origins is an important physiological process. Such cell fusion and horizontal gene-transfer events have also been linked to several fundamental features of cancer and could be important in the development of the cancer stem cell.

Epigenetics and the plasticity of differentiation in normal and cancer stem cells

“…It has recently been emphasized that cancer therapy should include the targeting of cancer stem cells (Singh et al, 2003;Valk-Lingbeek et al, 2004;Behbod and Rosen, 2005;Bjerkvig et al, 2005;Bonnet, 2005). Although cancer cells can be derived from normal self-renewing stem cells, more differentiated normal cells can also give rise to tumors (Cozzio et al, 2003;Castor et al, 2005).…”

Rb is dispensable for self-renewal and multilineage differentiation of adult hematopoietic stem cells

“…The ''Rb pathway'' is universally inactivated in human cancer (8). It is thought that during transformation the tumor-initiating cell, or cancer stem cell as it has become termed, develops many properties that are shared by nonneoplastic stem cells, such as the capacity to self-renew (9)(10)(11)(12). Understanding the role(s) Rb plays in the normal regulation of self-renewal may provide important insights into its role in transformation.…”

The shock of being united and symphiliosis

“…[65][66][67] Of particular interest are the possibilities that fusion of neoplastic cells to normal stem cells. 66,80,81 or extinction resulting from fusion of different cell types is a source of cancer stem cells. If plant evolution is any guide, even if cell fusion is by far more rare in the body than other pathways to polyploidy, and the majority of the resulting allopolyploids vanish, having emergent properties can make the survivors more consequential for the emergence and progression of the disease.…”