Novel markers for circulating tumor stem cells in colorectal carcinoma.

Some colorectal carcinoma (CRC) invades into vessels and has distal metastasis, largely attributable to the dissemination of tumor cells into circulation as circulating tumor cells (CTCs). Moreover, cancer stem cells (CSCs) within CTCs, which are termed as circulating tumor stem-like cells (CTSCs), are critical for formation of distal metastatic tumors. Although different cell surface markers have been used to characterize and isolate CTCs or CSCs in CRC, no good marker has been identified so far for CTSCs. Here, we show evidence that CD262+ CRC cells appeared to be highly enriched for CTSCs in CRC. CD262+ CRC cells formed more tumor spheres in culture, exhibited higher chemo-resistance, had higher ratio of developing tumors after serial adoptive transplantation in nude mice, and had higher frequency of developing distal metastatic tumor, compared to traditional CD133+ or CD44+ CRC cells. Moreover, tumor cells were significantly more frequently detected in the circulation when CD262+ CRC cells were subcutaneously transplanted. Finally, we detected high CD262 levels in the stage IV CRC specimens, which were associated with poor prognosis of the patients. Together, these data suggest CD262+ may be a novel CTSC markers and selective elimination of CD262+ CRC cells may substantially improve the current CRC therapy.