| Hepatocellular carcinoma(HCC)is one of the most common malignant tumors in China,the overall survival time of patients with hepatocellular carcinoma is relatively short.Nowadays,surgical resection is the best therapeutic method for patients with HCC,but it is only suitable for part of them(approximately 10%-20%)with a high recurrence rate.So there is an urgent need to find new therapeutic targets for HCC.What closely related to the occurrence and development of HCC is chronic inflammation in liver with the process of malignant transformation from hepatitis and cirrhosis to HCC.The relationship between chronic inflammation and HCC has been widely accepted,but the mechanism still needs further study.CD47(Cluster of Differentiation 47)is a glycoprotein which is expressed commonly in human cell surface and belongs to the immunoglobulin superfamily.CD47 is also known as integrin associated protein(IAP)because it can be coprecipitated with integrin?v?3.The expression level of CD47 is up-regulated in many kinds of tumors and it plays an important role in the occurrence and development of HCC.CD47 interacts with signal-regulatory protein alpha(SIRP?)to inhibit the anti-tumor immunity in host induced by macrophage and help tumors escape from immune surveillance.In many cancer researches,scientists found that CD47 monoclonal antibody could be used to inhibit the growth of tumors in vivo effectively with little effect on normal cells.The above results suggest that CD47 may be a potential molecular target for tumor therapy.It is generally believed that the treatment effect of CD47 monoclonal antibody is related to the block of CD47 mediated the inhibition of phagocytosis.The role of CD47 in the progression of HCC is still at a preliminary stage.It has been reported that CD47 is involved in the regulation of the survival and function of liver cancer stem cells,but the mechanism involved in it is still unknown.Oxidative stress occurs when production of reactive oxygen species(ROS)exceeds the capacity of the cellular defense system consisting of redox enzymes and other antioxidant molecules to maintain redox status.Some tumor stem cells harbor only low levels of ROS and manifest enhanced mechanisms for protection against ROS-mediated damage,properties that may contribute to tumor resistance to chemo and radiotherapy.In these mechanisms,reduced glutathione(GSH)is a major cellular metabolite and expression of system xc-at the cell surface is essential for the synthesis of GSH.System xc-is a cystine-glutamate exchange transporter composed of a light-chain subunit(SLC7A11,solute carrier family 7 member 11)and a heavy-chain subunit(SLC3A2,solute carrier family 3 member 2).SLC3A2 associates with integrins and mediates integrin-dependent signaling related to normal cell growth and tumorigenesis.We speculate that SLC3A2 may have some relationship with CD47.In our study,first,we analyzed the expression level of CD47 on HCC specimens,and then we explored the related factors which can regulate the expression of CD47.We investigated the biological effect of CD47 on HCC with multiple methods and we found CD47 can regulate redox status in HCC.Next,we searched for the molecular mechanism for the purpose of finding the reason why CD47 can have such a significant biological effect on HCC.Our data showed that the expression level of CD47 was high on HCC specimens and the expression level increased with the progression of disease in DEN-induced HCC model.Inflammatory factor TNF? can elevate the expression level of CD47 by activating NF-?B signaling pathway.CD47 promoted the malignant phenotype of HCC by decreasing the level of ROS in cells.And then we found that CD47 regulate redox status by interacting with SLC3A2. |
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