Identification of human cutaneous squamous cell carcinoma cancer stem cells

Abstract

Epithelia are under constant threat from environmental carcinogens and none more so than squamous epithelia, which form the outermost linings of our bodies. Hence malignancies of squamous epithelia are collectively the most common cancer type and with the highest mortality, despite a constant cell turnover and only relatively rare long-lived adult tissue stem cells. Genetic analysis from SCC whole genome sequencing reveals commonality in mutated genes, despite various etiological factors. Most SCC types have been shown to exhibit hierarchical growth, in which a high frequency of cancer stem cells is associated with poor prognosis. For human cutaneous SCC (cSCC), we have shown that cancer stem cells express CD133 and that this population can recreate tumor heterogeneity in a novel in vivo model. CD133+ cSCC cells is small subset of tumor cells (~1%) in the outer layer of cSCC that are highly enriched for tumor-initiating capacity (TIC) (~1/400) compared to unsorted cSCC cells (~1/106). Xenografts of CD133+ cSCC recreated the original cSCC tumor histology and organizational hierarchy, while CD133- cells did not. Only CD133+ cells demonstrated the capacity for self-renewal in serial transplantation studies. Hence, cSCC has the potential to be the ideal model in which to study SCC biology.