Cancer stem cells: A product of clonal evolution?

Abstract

The cancer stem cell (CSC) model has emerged as a prominent paradigm for explaining tumour heterogeneity. CSCs in tumour recurrence and drug resistance have also been implicated in a number of studies. In fact, CSCs are often identified by their expression of drug-efflux proteins which are also highly expressed in normal stem cells. Similarly, pro-survival or proliferation signalling often exhibited by stem cells is regularly reported as being upregulated by CSC. Here we review evidence suggesting that many aspects of CSCs are more readily described by clonal evolution. As an example, cancer cells often exhibit copy number gains of genes involved in drug-efflux proteins and pro-survival signalling. Consequently, clonal selection for stem cell traits may result in cancer cells developing "stemness" traits which impart a fitness advantage, without strictly following a CSC model. Finally, since symmetric cell division would give rise to more cells than asymmetric division, it is expected that more advanced tumours would depart from a CSC. Collectively, these observations suggest clonal evolution may explain many aspects of the CSC.

Epigenetic age acceleration of cervical squamous cell carcinoma converged to human papillomavirus 16/18 expression, immunoactivation, and favourable prognosis

“…Such findings were reasonable for normal tissue because accelerated DNAm age-meaning that the individual older biologically than chronologically-is often induced by unhealthy lifestyles, susceptible heredity, harmful environmental exposures, or other stochastic events, while this might not be the case for cancerous tissue. Notably, carcinogenesis is an evolutionary process with sequential steps, including somatic mutations, subclonal evolution, and formation of cancer stem cells which possess the ability to proliferate and propagate [40,41]. Similar to normal cells, the DNAm age of cancer cells increases with propagation, which indicates that cancer cells with The DNAmAge-ACC* group was predicted to have a higher likelihood of responding to paclitaxel and gemcitabine than DNAmAge-DEC* group, which is shown in (c) and (d), respectively; DNAmAge-ACC* presented with significantly higher HPV pca scores and lower tumour mutation load than DNAmAge-DEC* group in (e) and (f), respectively.…”

Breast cancer stem cells as last soldiers eluding therapeutic burn: A hard nut to crack

“…Further, CD24 has been found to be heavily glycosylated that can bind to P‐selectin expressed on Additionally, CD44 is also defined as a transmembrane glycoprotein with a clear role in cell‐cell and cell‐matrix adhesion interactions, and cell migration. However, there are certain controversies regarding the claim that CD24 is not a consistent breast cancer stem cell marker and its direct role in tumorigenicity is not convincing . Further, evidence suggests that the CD44+/CD24−/low phenotype may not be sufficient to characterize BCSCs .…”

“…However, there are certain controversies regarding the claim that CD24 is not a consistent breast cancer stem cell marker and its direct role in tumorigenicity is not convincing . Further, evidence suggests that the CD44+/CD24−/low phenotype may not be sufficient to characterize BCSCs . There are reports on the expression of integrins such as CD29 (β1), CD49f and CD61 (β3), which are only marginally expressed in normal mammary epithelia .…”

“…Several experimental data suggest that CD133 named as prominin‐1 is recognized in a subgroup of breast CSC. Also the expression level ofCD131 has been found to be more distinct in BCSCs in comparison with other CSC markers such as CD44 and ALDH . Another BCSC marker, which is reported as aldehyde dehydrogenase (ALDH) enzyme has been shown to be involved in the detoxification process.…”

“…TG2 is reported to be an important breast cancer cell survival factor and is a marker for high risk cancer recurrence . Among cancer stem cell (CSC) molecular markers, several are being considered for their use as potential targets for developing new therapies to impede regeneration of CSCs and cancer relapse …”