To investigate the relationship between stem cells in normal epithelium and in squamous cell carcinomas (SCCs), we examined expression of a panel of human epidermal stem cell markers in SCCs and SCC cell lines. Markers that are co-expressed in normal stem cells were not co-expressed in SCC. Downregulation of two markers, Lrig1 and MAP4, and upregulation of a third, MCSP, correlated with poor differentiation status and increased proliferation in primary tumours. We conclude that SCCs do not reflect a simple expansion of stem cells; rather, tumour cells hijack the homeostatic controls that operate in normal stem cells, eliminating those that maintain stem cell quiescence.Last paragraph of the Discussion section:
In conclusion, our data favour a model whereby during tumour development the pathways that control epithelial homeostasis are lost, particularly in the basal cell layer closest to the tumour stroma. Those markers of normal stem cells that exert a positive effect on proliferation or inhibit differentiation are upregulated, while those that normally retain the cells in a nondividing state show reduced expression. As we find out more about how different signalling pathways intersect to maintain homeostasis we will have more opportunities for restoring homeostasis in tumours.[This is a Sponsored Article. The PMC version may be redistributed and reused, subject to certain conditions].