The CSCs co expressing CXCR4 were cancer cells with a migratory and invasive phenotype in pancreatic http://www.selleckchem.com/products/Tipifarnib(R115777).html cancer. In specimens from CRC patients,Pang et al. demon strated the existence of migratory CSCs with the CD26 surface antigen as a marker. In this study, we deter mined that the percentage Inhibitors,Modulators,Libraries of CD133CXCR4 cancer cells in metastatic liver tumors was nearly eight times higher than that in primary colorectal tumors, indicating Consistent results were obtained by the standard tail vein metastatic assay in vivo. This indicated that CD133 a metastatic phenotype. To evaluate the metastatic capa city of different subpopulations, we employed the tail vein metastasis model, which is also known as the experi mental metastasis model.

The limitation of this model lies in the fact that it cannot reflect the complete meta static process as does the spontaneous metastasis model in which the tumor cells are injected into the liver and allowed to first form a primary tumor. The complete metastasis cascade includes the following steps escape Inhibitors,Modulators,Libraries of cells from the primary tumor, entry of cells into the lym phatic or blood circulation, survival and Inhibitors,Modulators,Libraries transport in circulation, escape of cells from circulation, and growth of cells to form secondary tumors in a new organ environment. However, the tail vein metastasis model is able to mimic the extravasa tion of cancer cells from blood vessels in the target organ which is regarded as a critical step in the metastatic pro cess. Therefore, as in many studies, it is suf ficient to use this model for the comparison of metastatic capacity among different groups.

EMT results in morphological and molecular changes that occur when epithelial cells lose their characteristics and gain mesenchymal properties. The expression of mesenchymal markers, such as N cadherin and vimentin, and the loss of E cadherin are key molecular events of EMT. Transcription factors, such as Snail and Twist, bind to consensus E box sequences in Inhibitors,Modulators,Libraries the E cadherin gene pro moter and down regulate E cadherin transcription. The association between EMT and CSC has been reported previously. Several studies have provided evidence showing that CSCs express EMT markers and that induction of EMT could convert epithelial cells into breast CSCs. This demonstrates the essential role of EMT in CSCs acquiring invasive and metastatic phenotypes.

We have proven our hypothesis that EMT is involved in the origin of migratory CSCs in colon cancer, using real time RT PCR to determine EMT related gene expression. Pang et al. reported that EMT like attributes contribute to the invasive phenotype and metastatic capacity of the migra tory subpopulation in Inhibitors,Modulators,Libraries CRCs. This is in line with our findings that the corresponding alteration in mRNA expression levels Dasatinib mechanism of EMT related genes and higher migra tory and invasive capacities have been observed in CD133 CXCR4 cancer cells.