Cancer Stem Cells: Emergent Nature of Tumor Emergency

Abstract

A functional analysis of 167 genes overexpressed in Krebs-2 tumor initiating cells was performed. In the first part of the study, the genes were analyzed for their belonging to one or more of the three groups, which represent the three major phenotypic manifestation of malignancy of cancer cells, namely (1) proliferative self-sufficiency, (2) invasive growth and metastasis, and (3) multiple drug resistance. 96 genes out of 167 were identified as possible contributors to at least one of these fundamental properties. It was also found that substantial part of these genes are also known as genes responsible for formation and/or maintenance of the stemness of normal pluri-/multipotent stem cells. These results suggest that the malignancy is simply the ability to maintain the stem cell specific genes expression profile, and, as a consequence, the stemness itself regardless of the controlling effect of stem niches. In the second part of the study, three stress factors combined into the single concept of “generalized cellular stress,” which are assumed to activate the expression of these genes, were defined. In addition, possible mechanisms for such activation were identified. The data obtained suggest the existence of a mechanism for the de novo formation of a pluripotent/stem phenotype in the subpopulation of “committed” tumor cells.

Role of prostate cancer stem-like cells in the development of antiandrogen resistance

“…Extensive work has shown that CSCs from primary prostate tumors or established cancer cell lines can be isolated from a heterogeneous population using cell surface markers, such as CD44 and CD133, aldehyde dehydrogenase (ALDH) activity using the ALDEFLUOR assay, and Hoechst dye to identify the side population [ 62 - 63 ] . Isolation of prostate CSCs has been performed by several groups.…”

DNA Damage Response and Oxidative Stress in Systemic Autoimmunity

“…The high intracellular oxidation status in viral infections consists of decreased antioxidant enzymes such as catalase, glutathione peroxidase, glutathione reductase, as well as high levels of hydroxyl radicals. Of note, tumor growth and development is always accompanied by oxidative stress, which develops due to various inflammatory and immune reactions [80].…”

Identification of the xenograft and its ascendant sphere-forming cell line as belonging to EBV-induced lymphoma, and characterization of the status of sphere-forming cells

“…Nevertheless, the most important feature of CSCs, which distinguishes them from normal stem cells fundamentally, is their metastasizing capability that allows these cells to form the stromal microenvironment suitable for further development of tumor regardless of the initial cellular environment. This attribute is primarily associated with an ability of CSCs to retain a pluripotency outside the specific niches while being resistant to stemness-suppressing influence of normal tissue stroma [43], and determined by changes in expression of genes responsible for epithelial-to-mesenchymal transition [44][45][46].…”