The above data indicate that the CD133CXCR4 subpopulation contri butes to liver metastasis of colorectal cancer via EMT. Consistent with our findings, Esther and colleagues demonstrated that transforming more growth factor b induced the EMT process and de differentiation in Fao rat hepatoma cells. This process coincided with upregulated CXCR4 expression and also sensitization of these cells to respond to SDF 1, which mediated migration. Similar results were observed in oral squamous cell carcinoma. However, the reason cancer cells that have under gone EMT have a higher expression Inhibitors,Modulators,Libraries of CXCR4 is far from clear. Exploring the origin of migratory CSCs warrants further research and requires integration of current tumor initiation and progression concepts, including CSC, EMT, accumulation of genetic alterations and the tumor envir onment as driving forces.
A deeper understanding of these factors could provide further insights into tumor biology. The CSC hypothesis suggests that CSCs are a minority population that has the potential to self renew, Inhibitors,Modulators,Libraries differenti ate and regenerate a phenocopy of the original tumor. They would seem the most probable candidates that are resistant to chemotherapy, and they have been investigated previously. Novel treatments targeting CSCs may result in the complete eradication of tumor growth, and furthermore, based on the migratory CSC theory, if treatment targeting migratory CSCs can be developed, it might be possible to prevent tumor metastasis. We hypothesized that blockade of the SDF 1CXCR4 axis might suppress colon cancer metastasis to the liver, with the knowledge that the liver secretes Inhibitors,Modulators,Libraries high amounts of SDF 1.
This is also in line with the theory that organs producing SDF 1 attract CXCR4 tumor cells and form metastatic tumors analogous to the directed homing of leukocytes. In our study, a nude mouse hepatic metastasis model was employed, and the results indicated that chemi cal inhibition of CXCR4 with AMD3100 could inhibit colon cancer metastasis to the liver. The anti metastasis effect caused Inhibitors,Modulators,Libraries by the blockade of the SDF 1CXCR4 axis is supported by another report. This finding provides Inhibitors,Modulators,Libraries important clues for the development of a targeted therapy in the treatment of CRC. To validate the above findings in in vitro experimental and in animal models, we carried out a prospective study to investigate whether CD133CXCR4 cancer cell con tent was associated with disease progression and prog nosis.
Statistical analysis showed that high CD133CXCR4 cell content is associated with poor 2 year survival of colorectal cancer patients. www.selleckchem.com/products/crenolanib-cp-868596.html The clinical data provide evi dence to support our hypothesis that double positive can cer cells might be involved in the metastatic process. Our data showed that cancer located in the rectum was asso ciated with a high content of CD133CXCR4 cancer cell compared with colon cancer.