Mechanism Of Vascular Endochelial Growth Factor(Vegf) Promoting Lymphoma Cells Aggressive

Objective: To study the relationship between VEGF in NHL serum and patient's treatment effect and prognosis. The effects of VEGF on lymphoma cell's malignant phenotype (including ultrastructure, cytoskeleton), on the expression of hetertypic adhesion molecule CD44v6 and of p-glycoprotein were studied. The mechanism of VEGF affecting patients with lymphoma on prognosis and treatment effect was studied. Methods: After culturing lymphoma cells induced by VEGF for 2 h, the ultrastructure change on the surface of lymphoma cells was observed with electric microscope, the change of cytoskeleton, CD,, expression with laser confocal microscope, P-gp protein expression with Fluorescence activated cell sorter (FACS). Results: We observed the ultrastructure of Raji cells treated with VEGF under the HITACH-600 microscope. There were more and longer filopodia and microvillus on the surface of the cells, some cells were seen with swelled filopodia in the end. It was found that, microsilk F-actin of cytoskeleton in Raji cells surrounded the nucleus and arranged on the outer cycles of cells, F-actin of skeleton cells were destroyed, the amount of stress fibre decreased microsilk F-actin in Raji cell induced by VEGF for 2 h gathered and formed into capping structure. It was observed that CD44v6 was situated at the surface of lymphoma cells, fluorescent intensity of the controlled group cells was lower than that of trial group cells which was cultured with VEGF for 2 h, there was significant difference between two groups, P<0.01. VEGF can increase the amount of CD44v6 expression. We detected quantity of P-gp three times in every sample with FACS and calculated mean value of the three samples. The result showed that, the number of positive cells in control group is 2.7% +/- 0.45%, the number of positive cells induced by 5 mug/mL VEGF is 16.47% +/- 3.5%. The number of positive cells induced by 5 mug/mL VEGF is marked higher than that in blank control group and control group, P<0.01. Conclusion: There are longer filopodia and more microvillus on the surface of lymphoma cell's induced by VEGF, it may promote capability of lymphoma cell's migration and movement, and enhance malignant degree of lymphoma cell's. Capping structure on surface of the lymphoma cell membrane is helpful for increasing lymphocyte cell's ability to home lymph tissue, VEGF can promote the capping formation of lymphoma cells cytoskeleton. It is concluded that VEGF promotes lymphoma cells invasion and metastasis through increasing expression of CD44v6 which is called homing receptor, and enhances expression of affecting chemotherapy effect P-gp protein in lymphoma cells, which leads patient with NHL to resistance and poor prognosis.