Cancer Stem Cells: Cellular Plasticity, Niche, and its Clinical Relevance

Abstract

Cancer handles an estimated 7.6 million deaths worldwide per annum. A recent theory focuses on the role Cancer Stem Cells (CSCs) in driving tumorigenesis and disease progression. This theory hypothesizes that a population of the tumor cell with similar functional and phenotypic characteristics as normal tissue stem cells are responsible for formation and advancement of many human cancers. The CSCs subpopulation can differentiate into non-CSC tumor cells and promote phenotypic and functional heterogeneity within the tumor. The presence of CSCs has been reported in a number of human cancers including blood, breast, brain, colon, lung, pancreas prostate and liver. Although the origin of CSCs remains a mystery, recent reports suggest that the phenotypic characteristics of CSCs may be plastic and are influenced by the microenvironment specific for the individual tumor. Such factors unique to each tumor preserve the dynamic balance between CSCs to non-CSCs cell fate, as well as maintain the proper equilibrium. Alternating such equilibrium via dedifferentiation can result in aggressiveness, as CSCs are considered to be more resistant to the conventional cancer treatments of chemotherapy and radiation. Understanding how the tumoral microenvironment affects the plasticity driven CSC niche will be critical for developing a more effective treatment for cancer by eliminating its aggressive and recurring nature that now is believed to be perpetuated by CSCs.

The role of TRIM family proteins in the regulation of cancer stem cell self-renewal

“…Functional and phenotypical properties of these cells are substantially influenced by genetic, epigenetic, and microenvironmental factors. 18,20,21 Because of their high plasticity, CSCs may experience phases of transition between stem-like and non-stem-like states. 18,20,21 Therefore, the concept of CSCs has to be redefined.…”

“…18,20,21 Because of their high plasticity, CSCs may experience phases of transition between stem-like and non-stem-like states. 18,20,21 Therefore, the concept of CSCs has to be redefined. A growing body of evidence demonstrates that bulk tumor cells can acquire stem cell properties in response to exogenous stimuli.…”

“…This suggests that the process of cancer cell differentiation can be reversed and further adds to the complexity of cancer stemness. 19,20 In this review, we have considered the stemness of cancer cells as a specific state a cancer cell can achieve and maintain and characterized the mechanisms that regulate this phenomenon. Among others, the activation of specific signaling pathways and the induction of several transcription factors play a fundamental role 18,22 in the regulation of stem cell pluripotency.…”

Increased Cellular Levels of MicroRNA-9 and MicroRNA-221 Correlate with Cancer Stemness and Predict Poor Outcome in Human Breast Cancer

“…By contrast, knockdown of miR-9 and miR-221 led to decreased production of SP cells and resulted in decreased invasiveness of MDA-MB-231 breast cancer cell line. Similarly, in studies of recurrent glioma, SP cells were screened for hierarchical organization within the new tumor clone because this subpopulation has stem cell-like characteristics and plasticity that are critical for tumor reprogramming to a more aggressive tumor phenotype [25,26]. Taken together, these findings provide evidence for a causal link between the regulatory role of miRNAs in establishing the cancer stemcell phenotype, highlighting the relevance of differential expression of such miRNAs in a paradigm that distinguishes between benign and invasive features of carcinomas, including those of breast cancer, based on the generation of SP cells.…”

Impact of perioperative pain management on cancer recurrence: an ASRA/ESRA special article

“…Based on recent hierarchical theory of cancer genesis, tumor progression appears to be linked to a subset of tumor cells known as “cancer stem cells” residing in a specific environment within the tumor microenvironment called the cancer stem cell niche 16. These cells have the capacity for self-renewal, tumor initiation potential, and long-term tumor reinitiating function.…”