Cancer Stem Cells – Basic Biological Properties and Experimental Approaches

Abstract

Cancer stem cells (CSCs) are defined as a self‐renewing and self‐protecting subpopulation of tumour cells that can differentiate into all other tumour cell types found within a tumour. They can be prospectively identified and purified, either on the basis of specific cell surface marker expression, or by virtue of their biological properties; their self‐protection has been harnessed to develop several purification strategies, for example, side population or Aldefluor assays. Other prominent biological properties of CSCs include their exclusive clonogenicity and tumourigenicity. Many of these basic biological characteristics are shared between normal and CSCs, as are multiple signalling pathways regulating self‐renewal and differentiation. Unlike normal stem cells, CSCs often seem to be distinctly less stable, dynamically modulating their stemness and differentiation according to various environmental signals and/or genetic and epigenetic changes accumulated during the carcinogenic process. This plasticity of CSCs might underlie the prominent biological characteristics of malignant tumours, especially their propensity to metastasise. Key Concepts: Stem cells are long‐lived and protect their genome. Existence of long‐lived, undifferentiated and self‐protecting cells could be indirectly inferred in tumours. Cancer stem cells express specific cell surface markers and are amenable to differential staining procedures. Cancer stem cells frequently exploit similar signalling pathways as embryonic stem cells and normal adult stem cells. Hypoxia activates a multifaceted stem cell programme in tumours. Cancer stem cell phenotype can be unstable, with repeated or even ongoing differentiation and dedifferentiation.

Complex Interplay of Genes Underlies Invasiveness in Fibrosarcoma Progression Model

“…Apparently, the clonogenicity in a semisolid medium may reflect a combination of the proliferative activity and evasion from anoikis, and the overall excellent correlation between the steepness of growth curves in a classical two-dimensional culture and the clonogenicity in methylcellulose suggests that the general proliferative activity could indeed be essential for the anchorage-independent growth of the JUN-sarcoma cell lines. On the other hand, clonogenicity in semisolid media is also increasingly viewed as an assay for cancer stem cells [ 53 , 54 ], and in this case, differences in the clonogenicity in methylcellulose among the JUN-sarcoma cell lines could be more indicative of differences in a relative frequencies of sarcoma stem cells. To resolve this question, we performed the sarcosphere assay ( Figure 4 E,F, Table S3 ).…”