Differences and similarities between cancer and somatic stem cells: therapeutic implications

Abstract

Over the last decades, the cancer survival rate has increased due to personalized therapies, the discovery of targeted therapeutics and novel biological agents, and the application of palliative treatments. Despite these advances, tumor resistance to chemotherapy and radiation and rapid progression to metastatic disease are still seen in many patients. Evidence has shown that cancer stem cells (CSCs), a sub-population of cells that share many common characteristics with somatic stem cells (SSCs), contribute to this therapeutic failure. The most critical properties of CSCs are their self-renewal ability and their capacity for differentiation into heterogeneous populations of cancer cells. Although CSCs only constitute a low percentage of the total tumor mass, these cells can regrow the tumor mass on their own. Initially identified in leukemia, CSCs have subsequently been found in cancers of the breast, the colon, the pancreas, and the brain. Common genetic and phenotypic features found in both SSCs and CSCs, including upregulated signaling pathways such as Notch, Wnt, Hedgehog, and TGF-β. These pathways play fundamental roles in the development as well as in the control of cell survival and cell fate and are relevant to therapeutic targeting of CSCs. The differences in the expression of membrane proteins and exosome-delivered microRNAs between SSCs and CSCs are also important to specifically target the stem cells of the cancer. Further research efforts should be directed toward elucidation of the fundamental differences between SSCs and CSCs to improve existing therapies and generate new clinically relevant cancer treatments.

MicroRNAs and Stem-like Properties: The Complex Regulation Underlying Stemness Maintenance and Cancer Development

“…Of interest, cell-derived microvesicles isolated from MSCs also contain patterns of miRNAs specifically expressed by MSCs (miR-103-1, -140, -143-5p, and -340), which are specific to cell origin and represent a peculiar signature for adult stem cells [267]. Moreover, the different expression of exosome-delivered microRNAs between somatic stem cells and CSCs also represents a good way to specifically identify the CSCs [268]. Indeed, the aberrant expression of microRNAs normally expressed in adult stem cells can be responsible for cancer development.…”

Exosomes and Cancer Stem Cells in Cancer Immunity: Current Reports and Future Directions

“…Recent studies have proposed superior tumor growth inhibitory effects by targeting CSCs rather than the whole tumor [106]. Thus, potential strategies for targeting CSCs by delivering miRNAs to inhibit the EMT or the formation of premetastatic niches have been thoroughly researched [107]. Neutralizing antibodies, or antibody-mediated CSC therapies, aim to target CSCs in various cancers to attenuate the stemness phenotype of these cells [107].…”

“…Thus, potential strategies for targeting CSCs by delivering miRNAs to inhibit the EMT or the formation of premetastatic niches have been thoroughly researched [107]. Neutralizing antibodies, or antibody-mediated CSC therapies, aim to target CSCs in various cancers to attenuate the stemness phenotype of these cells [107]. Exosome signaling is also known to induce the production of CSCs, ameliorate treatment resistance, and prevent tumor relapse [108].…”

Glucose and Amino Acid Metabolic Dependencies Linked to Stemness and Metastasis in Different Aggressive Cancer Types

“…CSCs share some properties with normal adult stem cells, such as: 1) specific gene expression ( Ginestier et al, 2007 ), 2) division by generating a CSC (self-renewal) and another cell that can later differentiate to diverse malignant cell types in a given tissue, and 3) the activation of common signalling pathways that contribute to proliferation, self-renewal and survival/resistance ( Kanwar et al, 2010 ; Rossi et al, 2020 ). CSCs, however, differ from normal adult stem cells in that they remain fundamentally cancer cells and that the regulating mechanisms in normal stem cells are deregulated in CSCs.…”

“…CSCs, however, differ from normal adult stem cells in that they remain fundamentally cancer cells and that the regulating mechanisms in normal stem cells are deregulated in CSCs. This leads to the continuous expansion and production of an aberrantly differentiated progeny: the tumour ( Rossi et al, 2020 ). To complicate matters, CSCs are also thought to be generated by pre-malignant or malignant cells via a process of de-differentiation that makes tumour cells resemble embryonic cells to some extent.…”