Identification and characterization of tumor initiating cells in human primary cutaneous squamous cell carcinoma

Primary human squamous cell carcinoma (SCCa) are heterogeneous invasive tumors with proliferating outer layers and inner differentiating cell masses. To determine if tumor initiating cells (TIC) are present in SCCa, we utilized newly developed reliable in vitro and in vivo xenograft assays that propagate human SCCa, and demonstrated that a small subset of SCCa cells (~1%) expressing Prominin-1 (CD133) in the outer layers of SCCa were highly enriched for TIC (~1/400) compared to unsorted SCCa cells (TIC ~1/10(6)). Xenografts of CD133+ SCCa recreated the original SCCa tumor histology and organizational hierarchy, while CD133- cells did not, and only CD133+ cells demonstrated the capacity for self-renewal in serial transplantation studies. We present a model of human SCCa in which tumor projections expand with outer leading edges that contain CD133+ TIC. Successful cancer treatment will likely require that the TIC identified in cancers be targeted therapeutically. The demonstration that TIC are present in SCCa and are enriched in a CD133-expressing subpopulation to our knowledge has not previously been reported.