The Expression Of Midkine In Gastric Cancer And Its Clinical Significance

Midkine(MK) is a member of the heparin-binding growth factors, and is anovel growth differentiation factor. To date, it is known that MK is highlyexpressed in the mid-gestational period during embryogenesis, however, theexpression of MK in adult tissue is very restricted.In recent years,manyexperiments show that MK have important biological activities inchudingfibrinolytic, anti-apoptotic, mitogenic, transforming, angiogenic, andchemotactic ones.MK is detected in some kinds of human carcinomaspecimens. As to employing MK for gene therapy and as molecular target forcancer is currently being carried out in several laboratories.As we konw , it isthe first study that analyzed the expression of MK in gastric cancer in ourcountry.We examined the expression of the MK protein in specimens of 22 surgically removed human gastric carcinomas and 5 normal gastric tissue by immunohistochemical stain and wsetern blot analysis. The expression of MK protein in cancer tissues were examined with respect to tumor size, depth, clinical stage, differentiation, and node metastasis.The result of this study show:1.The expression of MK protein is not onlylocalized in the cytoplasm but also localized in nucleus of cancer cell. Weknow that nuclear targeting by extracellular signaling molecules such asgrowth factors. Yoshihisa,et al. recently demonstrated that MK bindslow-density lipoprotein receptor-related protein (LRP), and mediates nucleartargeting by indirect immunofluorescence staining. Internalized MK in thecytoplasm bound to N-terminal domain of nuceolin,a nucleocytoplasmicshuttle protein.They also demonstrated that the nuclear targeting is necessaryfor the full activity of MK in the promotion of cell surivial. We found theMK protein can localized in the nucleus of cancer cells byimmunohistochemical analysis(figure 5).It will be helpful to explain how MKis involved in carcinogenesis by futher research of MK nuclear targeting.2,The expression of MK in cancer specimens is significantly higher than in thecorresponding non-cancerous tissues and normal tissues .In this study, MKexpression was found in 59.1% (13/22) of 22 gastric cancer tissues and in9.1%(2/22) of corresponding non-cancerous tissues . While MK protein wasnot detected in the normal gastric tissues. The overexpression of MK proteindetermined by western Blot analysis was similar to that byimmunohistochemical analysis. No specific positivity was detected in normalgastric tissues. We demonstrated that the expression of MK in cancerspecimens is significantly higher than in the corresponding non-canceroustissues and normal tissues .This result is similar to the research of K.Aridome ,et al..3. The overexpression of MK protein significantly correlatedwith tumor size ,depth and clinical stage.In this study, MK expression wasfound in 33.3% (4/12) gastric cancers with a maximal diameter of 1-4cm...