Cancer stem cells: emerging actors in both basic and clinical cancer research

Abstract

IntroductionOver the past 50 years, many disease that cause death have dramatically decreased. Nevertheless, cancer deaths continue (Leaf, 2013). The International Agency for Research on Cancer, the specialized cancer agency of the World Health Organization, released the latest data on cancer incidence, mortality, and prevalence worldwide (Ferlay et al., 2013). According to GLOBOCAN 2012, an estimated 14.1 million new cancer cases and 8.2 million cancer-related deaths occurred in 2012, compared with 12.7 million and 7.6 million in 2008, respectively. The most commonly diagnosed cancers worldwide were those of the lung (13% of the total), breast (11.9%), and colorectum (9.7%). The most common causes of cancer death were cancers of the lung (19.4% of the total), liver (9.1%), and stomach (8.8%). GLOBOCAN 2012 predicted a substantive increase to 19.3 million new cancer cases per year by 2025 due to growth and aging of the global population (Ferlay et al., 2013). Despite these statistics, the ability to specifically target pathways altered in cancer raises the hope of developing therapies with high specificity and low toxicity. Therefore, it is important to target the 'right cells' (Wicha et al., 2006).A large body of evidence is accumulating to indicate that most, if not all, malignancies can be viewed as abnormal organs with a stem cell compartment that drives the growth. Furthermore, besides tumor initiation, these tumor-initiating cells, also referred to as cancer stem cells (CSCs), are thought to be responsible for metastasis, recurrence, and drug resistance (Chen K et al., 2013). The CSC hypothesis has fundamental implications for understanding the biology of carcinogenesis as well as for developing new strategies for cancer prevention and eradication of malignancies. Characteristics of CSCsCSCs are cancer cells that possess characteristics associated with normal stem cells. At the molecular level, CSCs and normal stem cells share some common features, including the capacity for self-renewal (Reya et al., 2001), the ability to differentiate, active telomerase expression, activation of antiapoptotic pathways, increased membrane transporter activity, and the ability to migrate and metastasize (Wicha et al., 2006). In addition to these properties, they display an anchorage-independent survival, active DNA-repair capacity, and relative quiescence (slow cell cycling) (Dean et al., 2005;Wicha et al., 2006). Concept of CSCsWhere CSCs come from is an intensely researched question. Some researchers suggest that CSCs may originate from mutated normal stem cells upon aberrant alteration of the self-renewal pathways (Reya et al., 2001). An alternative hypothesis is that CSCs originate from differentiated cells that have acquired stem-like features following Abstract: Cancer stem cells (CSCs) are a small subset of cancer cells within a tumor that are responsible for tumorigenesis and contribute to drug resistance. The CSC displays an anchorage-independent survival, active DNA-repair capacity, and relative quiescence and is ...

Review on Stem Cell Therapy and their Role in Cancer Treatment

“…Furthermore, it has also been demonstrated that cell surface markers could be dynamically and reversibly expressed by tumorigenic cells [46]. Therefore, it is clearly insufficient to define a cancer stem cell based solely on surface markers [11].…”

“…SP cells constitute a subpopulation of cancer cells that can efficiently efflux the fluorescent DNA binding dye, Hoechst 33342 and ATP binding cassette transporter [14]. Although the use of Hoechst 33342 dye enables identification of Hoechst-negative CSC SPs, the possible toxicity of the dye may cause side effects during cell sorting [11]. Small differences in cell densities, dye concentrations and staining timings may affect the phenotype of the SP cells [14].…”

“…ALDH is required for the oxidation of intracellular aldehydes thereby resulting in the oxidation of retinol to retinoic acid [14]. ALDHs belong to the oxido-reductase family, which oxidizes a wide range of endogenous and exogenous aldehydes to their corresponding carboxylic acid [11]. cytotoxic therapies induce DNA damage or disrupt mitosis leading to cell death in dividing cancer cells.…”

“…CSCs are isolated from primary tumors and cell lines by flow cytometry, fluorescence-activated cell sorting, or magnetic cell separation according to specific cell surface markers like CD133, CD44, CD24, CD34 and CD38 [11]. Biomarkers of the cancer stem cells not only the tools which are used to identify the cancer stem cells, but also might become the target of many drugs which were developed to cure cancer [17].…”

“…General methods for the identification and isolation of CSCs in malignancies include xenotransplantation assays which are the gold-standard for identification of CSCs; sorting based upon cell surface markers; efflux of Hoechst 33342 or Rhodamine dyes; the enzymatic activity of aldehyde dehydrogenase (ALDH) and colony and sphere forming assays requiring specific culture conditions [11]. Cancer stem cells reside in specialized microenvironments called niches, which have an important role in stem cell maintenance.…”