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

Abstract

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-1^high CRC, compared to Flt1^low 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.