Abstract
A B S T R A C T The digestive system encompasses several organs in which tumors occur with an elevated prevalence and mortality worldwide. Increasing evidence shows that cancer stem cells (CSCs) may play a critical role in tumor development and progression. In addition, CSCs are characterized by resistance to conventional therapies probably explaining why is difficult to completely eradicate cancer. Thus, the research on CSCs is critical to develop therapeutic strategies for a more effective reduction in the risk of relapse and metastasis and possible total elimination of tumors. This review compiles information about markers, signaling pathways and putative targeting of CSCs in several organs of the digestive system in order to unravel common and divergent patterns and behaviors that could be useful for future CSC research.
Highlights
The digestive system encompasses several organs in which tumors occur with an elevated prevalence and mortality worldwide
The levels of Sox2 are crucial for the balance between self-renewal and differentiation [12] as overexpression of this gene in the basal layer promotes hyperproliferation and cooperates with inflammation signaling (IL-6/Stat3) for the development of esophageal squamous cell carcinoma (ESCC). These findings suggest that basal stem/progenitor cells are the cells of origin of ESCC
In Hepatocellular carcinoma (HCC) cell lines, inhibition of Wnt pathway reduces the fraction of putative OV6+ cancer stem cells (CSCs) and its resistance to chemotherapy [70], suggesting that the pathway is important for the maintenance of some CSC features
Summary
The CSC model is supported by an increasing body of experimental evidence. Lineage-tracing experiments have provided formal demonstration of multi-lineage differentiation as a source of epigenetic diversity in cancer tissues [6]. These epigenetic alterations as well as the microenvironment might promote the evolution of CSCs into different clones simultaneously present in the tumor, but bearing distinct invasive potential, hypoxia endurance or susceptibility to chemotherapy. The CSC model has important implications for clinical oncology, as it provides a new conceptual framework for the development of prognostic biomarkers and the design of anti-tumor drugs
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