| Colon cancer is the third most common malignant tumor all over the world.It is estimated that about 1.2 million patients are newly diagnosed with colon cancer every year.Colon cancer is the third leading cause of cancer death in developing countries.The incidence rate of colon cancer is increasing gradually in parallel with people's dietary which has changed due to the improved lifestyle.The major target of the distant metastasis of colon cancer is liver.Therefore,liver metastasis of colon cancer has been regarded as a critical challenge for the clinical treatment of colon cancer and a major cause of the high mortality rate of colon cancer patients.Effectively inhibiting or preventing the metastasis of colon cancer to liver is an important method and breakthrough point to improve the survival rate of the colon cancer patients.Previous opinions suggested that liver metastasis of colon cancer was caused by the facts that the blood from colon returns to liver via portal venous system,as well as the compressions on the tumor during the surgical procedures.However,we found that although the clinical stages and treatment methods were similar,only a small proportion of the colon cancer patients developed liver metastasis.In light of “chemotaxis-homing theory”,we are wondering that whether there are some biological associations between the primary cancer and the liver tissues,which makes some certain kinds of patients easy to develop liver metastasis.Previous studies have shown that the CXC chemokine receptor family-4(CXCR4)expression is increased in several colon cancer cells,esp ecially the cells from the ones with liver metastasis,while the liver of the patients are found with endogenous CXCL12,and that CXCR4 is the only receptor for CXCL12.The specific interactions between CXCR4 and CXCL12 in the CXCR4-CXCL12 bio-axis could regulate the proliferation,adhesion,invasion,and migration of tumor cells,affect tumor angiogenesis,and influence the migration of tumor cells.CXCR4-CXCL12 bio-axis may be reason of liver metastasis of colon cancer.Blocking the CXCR4-CXCL12 bio-axis could inhibit the growth and metastasis of tumors;therefore,specifically inhibiting CXCR4-CXCL12 bio-axis could be a novel but promising method in treating cancer.Low molecular weight heparin(LMWH)is widely used in clinical practices in preventing and treating pulmonary embolism,lower limb vein thrombosis,and myocardial infarction.Recent studies have shown that LMWH could also improve the survival of cancer patients by inhibiting the migration of tumor cells.Although the exact anti-tumor mechanisms of LMWH are still unclear,it is clear that heparin could decrease the products of heparinase catalyzed reactions,and inhibit the binding of selectins to tumor angiogenesis factors(TAF)through regulating heparan sulfate proteoglycan(HSPG).Our studies show the molecule of CXCL12 also include the binding domain of heparin,while heparin could change the CXCL12 monomer-dimer from balance to CXCL12 dimer,reduce the interaction between CXCR4 and CXCL12,and thus inhibit the cell proliferation,adhesion,migration,and infusion induced by CXCL12.This method could not only prevent the tumor from liver metastasis but also benefit the perioperative patients.The present study aimed to investigate whether LMWH could affect the CXCR4-CXCL12 bio-axis and thus reduce the liver metastasis of colon cancer,and further investigate the underlying mechanisms.The results of the present study showed that LMWH could block the interactions between CXCR4 and CXCL12 and inhibit the liver metastasis of colon cancer.Therefore,chemokine CXCL12 and the corresponding receptor CXCR4 are promising new targets for the targeted therapy,early applying LMWH could help inhibiting the spread of colon cancer cells into liver as well as the growth of the cells,and thus could increase the survival rate of the patients,reduce the recurrence rate,improve the prognosis and the life quality of the colon cancer patients. |
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