Tumor-initiating cells (
TICs) are defined by their ability to form
tumors after
xenotransplantation in immunodeficient mice and appear to be relatively rare in most human
cancers. Recent data in
melanoma indicate that the frequency of
TICs increases dramatically via more permissive
xenotransplantation conditions, raising the possibility that the true frequency of
TICs has been greatly underestimated in most human
tumors. We compared the growth of human pancreatic, non-small cell lung, and head and neck
carcinomas in NOD/SCID and NSG mice. Although
TIC frequency was detected up to 10-fold higher in NSG mice, it remained low (<1 in 2500 cells) in all cases. Moreover,
aldehyde dehydrogenase-positive (ALDH(+)) and CD44(+)CD24(+) cells, phenotypically distinct cells enriched in
TICs, were equally tumorigenic in NOD/SCID and NSG mice. Our findings demonstrate that
TICs are rare in these
cancers and that the identification of
TICs and their frequency in other human
malignancies should be validated via primary
tumors and highly permissive
xenotransplantation conditions.