Understanding Cancer Cells of Origin in Cutaneous Tumors
January 2016
in “
Elsevier eBooks
”
basal cell carcinoma squamous cell carcinoma cancer cells of origin cancer stem cells adult stem cells genetically engineered mouse models lineage-tracing experiments hair follicle interfollicular epidermis Hh pathway inhibitors Wnt signaling Sox9 expression Ras mutations p53 mutations stem cell quiescence anagen induction melanocyte stem cells CRISPR/Cas9 BCC SCC CCOs CSCs GEMMs Hedgehog pathway inhibitors Wnt pathway Sox9 Ras p53 CRISPR
TLDR The document concludes that identifying the specific cells where skin cancers begin is important for creating better prevention, detection, and treatment methods.
The document from 2016 explores the origins of cutaneous tumors, particularly basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), emphasizing the role of cancer cells of origin (CCOs) and distinguishing them from cancer stem cells (CSCs). It suggests that adult stem cells are potential CCOs due to their self-renewal capabilities and that genetically engineered mouse models (GEMMs) and lineage-tracing experiments are useful for studying cancer development in vivo. The document reports that multiple stem/progenitor cells can act as CCOs for BCCs, with the hair follicle being the CCO for the nodular BCC subtype and the interfollicular epidermis for the superficial BCC subtype. It also notes that Hh pathway inhibitors treat BCC but resistance occurs in some patients, and that factors like Wnt signaling and Sox9 expression are crucial for BCC development. For SCC, hair follicle stem cells can serve as CCOs, with mutations in Ras and p53 being common. The document also suggests that stem cell quiescence suppresses tumor initiation and that the induction of anagen is necessary for SCC formation. It highlights the need for further research on melanocyte stem cells in melanoma initiation and suggests employing CRISPR/Cas9 for future studies. The importance of understanding the specific cellular origin of each cancer for developing prevention strategies, early detection biomarkers, and effective therapies is emphasized.
