We used nude mice hepatic metastasis assays to examine the effect of blocking CXCR4 with AMD3100 on hepatic metastasis of colon cancer. As shown in Figure 5, only the injection of CD133CXCR4 cells into the spleens of nude mice resulted in hepatic metastasis 45 days later, selleck chem Vismodegib while injection of CD133CXCR4 cells failed to result in the formation of metastatic liver tumors. Furthermore, application of AMD3100, a pharmacological CXCR4 receptor inhibitor, was able to suppress the metastatic tumor burden in nude mice. Our results indi cated that the SDF 1CXCR4 system might Inhibitors,Modulators,Libraries be a potential target for the effective treatment of hepatic metastasis of CRC. High CD133CXCR4 cell content is associated with poor survival We collected colorectal tumor specimens from 29 patients and determined the content of the CD133CXCR4 sub population using flow cytometry.
Patients were Inhibitors,Modulators,Libraries classified as having high or low CD133CXCR4 cell contents according to the average CD133CXCR4 cell percentage. The association of CD133CXCR4 cell content with var ious clinical characteristics was determined by correspond ing statistical methods. A high CD133CXCR4 cell content was significantly correlated with rectal tumors when compared with colon Inhibitors,Modulators,Libraries cancer, high TNM stages, and distant metastases as indicated by M status. There was no significant association between high CD133CXCR4 cell content and patient age, gender, T status, N status and tumor grade.
With overall median survival time being 580 days, the median survival time for patients with high CD133CXCR4 cell content was 489 days, and 710 days for patients with low CD133CXCR4 cell content by the Kaplan Inhibitors,Modulators,Libraries Meier method, indicating that patients with high CD133CXCR4 enrichment of this CSC subpopulation in metastatic liver tumors Inhibitors,Modulators,Libraries and their potential involvement in CRC metasta sis to the liver. Transwell migration and invasion selleck Dasatinib assay results indicated that the CD133CXCR4 subpopula cell content had decreased two year survival. Discussion CD133 has been used as a marker of tumor initiating cells in neural cancers and is also generally accepted as a CSC marker for colon cancer. However, there are some reports suggesting that CD133 cancer cells are not a true representation of CSCs in colon cancer. We found that CD133 colon cancer cells isolated from the HCT116 cell line had a greater clonogenic and tumorigenic ability than CD133 cells irrespective of CXCR4 expression. The in vitro and in vivo assays lend credence to the viewpoint that CD133 could be a marker for colon cancer tumor initiating cells. In 2005, Brabletz et al. proposed the concept that there are two forms of CSCs in tumor progression, namely sta tionary CSCs and migratory CSCs.