Effection Of HCMV Infected Macrophage On Invasion Of Malignant Glioma Cells

Human cytomegalovirus(HCMV), a ?-herpesvirus, as one of the major pathogens that cause congenital anomalies of the central nervous system. HCMV infects a wide range of population, specifically in China more than 90% of adults are infected with it. Increasingly researches show that there is close link between HCMV infection and tumor, as HCMV genes and proteins are found in a variety of tumor tissues like gliomas, colon cancer and so on.Previous tests by our group proved effections of HCMV on development and progression of gliomas. To further understand the mechanism between HCMV infection and glioma, a THP-1 derived macrophage model is set up in this paper using PMA as an inducer to induce THP-1 monocyte into macrophage. RT-PCR was used to detect expression of immediate early gene(IE) and late gene(UL99) of HCMV, the results shown that macrophage can fully express IE and UL99. By testing epidermal growth factors(EGF) of the HCMV-infected macrophages by ELISA(enzyme-linked immunosorbent assay), we find that HCMV-infected macrophage promotes EGF secretion. We co-culture macrophages and U87 cells and then infected with HCMV. Western-bolt was used to detect the change of expression of epidermal growth factor receptors(EGFR) on U87 cell. The results shown that, compared with the control group, the expression of EGFR on U87 cell which co-culture with HCMV-infected macrophage was enhanced(p<0.05). The Transwell invasion assay to detect the influence of HCMV-infected macrophage on the invasion ability of U87 cell shows more U87-infected cells of membrane can be detected in the HCMV-infected group than non HCMV-infected group. The Transwell results shown that, compared with the control group, the cells number of invasion were enhanced in HCMV-infected group(p<0.05). HCMV-infected macrophage can increase invasive potential of U87 cells. The Western-blot results shown that both the infected-HCMV group and control group have tested the expression of FAK and Tyr397 FAK, while the expression of Tyr397 FAK of HCMV-infected group is higher than control group(p<0.05). HCMV infected macrophages can up-regulate phosphorylation of FAK.This paper analyzes the effection of HCMV infected macrophages on glioma malignant behaviors, laying a theoretical foundation for further explanation to HCMV-infected molecular mechanisms and the relations between HCMV infection and tumors.