Stem Cells and Cancer Stem Cells

Abstract

The different organs in human organism are constituted by tissues with mature and specialized cells and its specific stem cells. Stem cells represent only a minuscule fraction of cells that constitute each tissue but they are the only cells with self-renewal capacity. The organ-specific stem cells have specific properties that maintain tissue integrity and are defined mainly by their capacity to undergo self-renewal, as well as differentiation into mature cell types that comprise each organ (Shipitsin & Polyak, 2008). The malignant neoplasias are believed to result from sequential mutations that can occur as a consequence of progressive genetic instability and/or environmental factors. An accordant observation in several investigations has been the association between deregulation of stem cells and carcinogenesis, because there are regulatory mechanisms of self-renewal in normal stem cells that also frequently regulate oncogenesis. In consequence, experimental and clinical evidences that have recently been accumulated support the hypothesis that cancer may arise from mutations in normal stem cell populations, and that these cells would be subject to ongoing genetic and epigenetic changes that could help to establish the disease. The cancer stem cell (CSC) hypothesis states that normal stem cells may be the cells of cancer origin, and that a specific subset of cancer cells with stem cell characteristics can give rise to a hierarchy of proliferative and progressively differentiated bulk of tumoral cells, leading to tumor initiation, progression, and recurrence. In fact, there are several investigations that recently have identified specific CSC markers showing similar expression profiles than the normal stem cells of same organ. Moreover, CSCs can be prospectively isolated based on expression of a specific molecule or combination of molecules, and have the ability to give rise to new tumors when xenografted in immunodeficient mice. Additional confirmations that stem cells can play a role in carcinogenesis are the homologies found between normal adult stem cells and cancer cells. Besides self-renewal capacity, these characteristics include the production of differentiated cells, activation of antiapoptotic pathways, induction of angiogenesis, resistance to apoptosis and drugs (due to active telomerase expression and elevated membrane transporter activity), and the ability to migrate and propagate (Wicha et al., 2006). Notwithstanding, different from normal adult stem cells that remain constant in number, CSCs can increase as the tumors grow, and originate the progeny that can be both locally invasive and/or colonize distant sites. Therefore, the consolidation of CSCs knowledge into our current view of multistep cancer development has important implications for defining the target population for therapeutical