Cancer Stem Cells: The Role of the Environment and Methods to Identify Them

Abstract

The study and investigation of cancer stem cells (CSCs) or tumour initiating cells (TICs) have received enormous attention over the last 15 years. CSCs are rare, quiescent and capable of self-renewing and maintaining tumour growth and heterogeneity. Better understanding of CSCs will lead to a new era of both basic and clinical cancer research, reclassification of human tumours and development of novel therapeutic strategies. Therefore, the biological properties of CSCs, the relevance of CSCs to cancer therapy, methodologies to identify them are essential in order to address real and efficacious therapeutic strategies to eradicate the cancer. Primary tumours are responsible for 10% of cancer deaths. In most cases, the main cause of mortality and morbidity is the formation of metastases in sites distant from tissue in which the primary cancer is formed. The cancer cell detach from primary tumour and, through blood and/or lymphatic vessels, colonises new sites in which forms the secondary tumour. Accumulating evidences suggest that a subpopulation of tumour cells with distinct stemlike properties is responsible for tumour initiation, invasive growth and possibly dissemination to distant organ sites (Reya et al., 2001; Brabletz et al., 2005). These few cells can divide asymmetrically, producing an identical daughter cell and a more differentiated cell, which, during their subsequent divisions, generate the vast majority of tumour bulk (Caussinus & Gonzalez, 2005; Clevers, 2005). Many names have been used to identify this subpopulation, but the term “Cancer Stem Cells” (CSCs) has received wide acceptance. CSCs hypothesis states that the cancer stem cell is a cell within a tumour possessing the capacity of self-renewal and to cause the heterogeneous lineages of cancer cells that comprise the whole tumour (Ailles & Weissman, 2007; Lobo et al., 2007). Experimentally, this population is identified by its ability to form new tumours through serial transplantations in immunodeficient non-obese diabetic (NOD)/severe combined immunodeficient (SCID) mice, re-establishing tumour heterogeneity (Sarry et al., 2011). There are two basic topics that underline the hypothesis that CSCs may originate from normal tissue stem cells. First of all, CSCs share many features with normal stem cells, including self-renewal, differentiation, drug resistance and migration capacity. Secondly, the longevity of stem cells make them susceptible to accumulate genetic and epigenetic damages in such a way to make them good candidates for the emergence of the neoplastic transformation.