Flt-1-positive cells are cancer-stem like cells in colorectal carcinoma.

Recent evidence demonstrates an essential role of cancer stem cells (CSCs) in cancer initiation, progression, migration, metastasis as well as chemo-resistance. Nevertheless, identification of CSCs in different cancers has not been succeeded, since such CSCs are typically lack of a specific and unique marker. Therefore, the current strategy is basically using one or several markers to enrich CSCs, or to isolate CSC-like cells. Here, we showed that in clinically obtained colorectal carcinoma (CRC) specimens, Flt-1, the type 1 receptor for vascular endothelial growth factor A, was significantly upregulated. Moreover, more distal metastasis and poorer patient survival were detected in Flt-1high CRC, compared to Flt1low subjects. Two CRC cell lines were then labeled with both luciferase and red fluorescent protein (RFP) reporters. We found that in both lines, compared to Flt-1- CRC cells, Flt-1+ CRC cells generated significantly more tumor spheres in culture, appeared to be more resistant to fluorouracil-induced apoptosis, were more detectable in the circulation after subcutaneous transplantation, and had a higher chances to generate tumor after serial adoptive transplantation. Thus, we conclude that Flt-1 may be used as a surface marker to enrich CSC in CRC. Selective elimination of Flt-1+ CRC cells may improve the therapeutic outcome.