The Effects Of E-selectin And ICAM-1 On The Adhesion Of Hepatocellular Carcinoma Cells And Endothelial Cells

Primary liver cancer(PLC)is one of the most common malignancies worldwide including China. About 1 million new cases of PLC have been found every year. Surgery remains the best way for a curative therapy of PLC . However,long-term survival remains unsatisfactory after resetction of PLC, and tumor recurrence and metastasis is the main obstacles to improve prognosis. Some researchment have indicate that most recurrence and metastasis of PLC occurred within 1-2 years after surgical resection ,and the relapse rate of PLC within 1 year is 20% to 64%;within 3 years can be as high as 75%-81%. Another dates have reported that the postoperative recurrence of PLC was 61.1% in five years , even in small hepatocellular carcinoma ,postoperative recurrence rate was 43.5% also. Therefore, further improvement of long-term survival after hepatic resection may depends on prevention and treatment of recurrent and metastatic tumor.The adhesion between tumor cells and vascular endothelial cells is one of the crucial procedures of tumor recurrence and metastasis, and the expression of cellular adhesion molecules(CAMs) plays a very important role. The adhesion between tumor cells and vascular endothelial cells is mediated by cellular adhesion molecules. E-selectin is one of the adhesion molecule families ,and can be expressed in activated endothelial cells,and its ligants sleX and sleA strongly expressed on most tumor cells.There is strong evidences that E-selectin receptor-lignad interactions contribute to the formation of metastasis.E-selectin also can be used as a prognosis factor of tumor-specific indicator, at the same time ,blocking the expression and activity of E-selectin can reduce the tumor's metastasis . Intercellular adhesion molecule-1(ICAM-1) is one of the immunoglobulin superfamilys(IGSFs), and expresses the surface of mononuclear cells, lymph cells, vascular endothelial cells and human tumor cells. ICAM-1 participates many intercellular signal transduction in physiological and pathological procedures,including the metastasis and growth of tumor cells.The natural ligand of ICAM-1 is leucocyte function-associated antigen-1(LFA-1). The elevated expression of ICAM-1, on the one hand, can promote the angiogenesis and the growth of tumor cells, on the other hand , can decrease the capability that lymph cells and natural killer cells recognize tumor cells, and participate in the course that the tumor escape from the immunologic surveillance. The serum solulable intercellular adhesion molecule-1(sICAM-1) alse plays a very important role in promoting the angiogenesis and escaping from the immunologic surveillance. The evidences show that the over-expression of ICAM-1 in the surface of large intestine carcinoma cells has close correlation with lymph nodes metastasis. The expression of ICAM-1 in the surface of leukemic cells has correlation with extravascular exudation and disease progression, and anty-ICAM-1 mAb can inhibit the exudation. The surface of gastric carcinoma cells highly express ICAM-1, and the sICAM-1 can promote hematogenic metastasis. The serum sICAM-1 level of PLC patients can response the development and metastasis and therapeutic effects of PLC in some extent,and may become a index of predicting recurrence,metastasis and curative effect of PLC.Other researchs indicate that the high espression of ICAM-1 is relevant to highly metastatic characteristics of hepatocellular carcinoma. The therapy of anti-adhesion may be a direction that prevent and cure recurrence and metastasis of tumor.Based on the above characteristics, we hypothesis that hepatocellular carcinoma cells can secrete some substance which can stimulate the expression of E-selectin and ICAM-1 on endothelial cells. The activated endothelial cells adhere to the hepatocellular carcinoma cells by the specific binding of E-selectin,ICAM-1 and their ligands sleX,sleA and LFA-1.The receptor-ligand interactions contribute to the recurence and metastasis of PLC. So blocking the expression of E-selectin and ICAM-1 is expected to inhibit the adhersion of hepatocellular carcinoma cells and endothelial cells ,thus it is hopeful to achieve the purpose of blocking the recurrence and metastasis of PLC.Objective : To investigate the expression of E-selectin and ICAM-1 in hepatic vein endothelial cells (ED25) and umbilical vein endothelial cells (ECV304). To study the role of E-selectin and ICAM-1 on the adhesion of hepatocellular carcinoma cells and endothelial cells. To select related possible anti-adhesion drugs to inhibit recurrence and metastasis of hepatocelluar carcinoma.Methods : Expression of E-selectin and ICAM-1 in hepatic vein endothelial cell (ED25) and umbilical veinendothelial cells (ECV304) is detected by real-time quantitative PCR. Adhesion between the HepG2 cells and ED25 or ECV304 is examined by solid phase adhesion assay in vitro. A number of drugs are tested for the affects on the tumor cell-endothelial adhesion.Results: E-selectin and ICAM-1 are high expressed on the surface of actived ED25 and ECV304,and can mediate the adhesion between HepG2 and ED25 or ECV304. Dexamethasone,tanshinone are able to block the adhesion between HepG2 and ED25 at low concentration.Conclusions : E-selectin and ICAM-1 can strongly express in the activated hepatic vein endothelial cells and umbilical vein endothelial cells. E-selectin and ICAM-1 are important molecules in the adhesion of hepatocellular carcinoma cells to endothelial cells. Dexamethasone,tanshinone can be hopefully used as anti-adhesion drugs to inhibit recurence and metastasis of hepatocelluar carcinoma.