Expression Of IL-8, SDF-1 And CXCR4 In Human Astrocytic Tumors And Its Relationship With Angiogenesis

Glioma is the most common tumor in the central nervous system. Angiogenesis plays an important role in tumor growth, invasion and progression. The process is precisely regulated by proangiogenic factors and antiangiogenesis inhibitors. In the recent years, chemokines and their receptors have been found to be crucial for angiogenesis. Our previous studies have shown that glioblastoma cell line U87 and tumor stem cells can produce interleukin-8(IL-8). When being activated by its ligand SDF-1, CXCR4 can stimulate the secretion of IL-8 and VEGF by glioma cells and tumor stem cells. For further study on the expression of IL-8 and SDF-1/CXCR4 axis in surgical specimens and the relationship with tumor angiogenesis, in this study, human glioma specimens on tissue microarray, laser scanning confocal microscopy, immunohistochemistry were used to detect chemokines IL-8 and SDF-1 and the clinico-pathological relationship was discussed. The main findings and conclusions are as follows:1. Construction of tissue microarray. The tissue microarray composed of 153 points were constructed with human astrocytoma tissues. The microarray includes different grades of astrocytoma and normal brain. IL-8, VEGF and CD34 were detected by using immunohistochemical staining. The results showed that the expression levels of IL-8 and VEGF were not related with age and sex, and were closed to the pathological grade in 45 patients with glioma grade III, IV are more than grade I , II .The expression levels of IL-8 and VEGF in 6 patiens with normal brain tissue are negative. IL-8 was major expressed in cytoplasm of tumor cells, occasionally in infiltrated inflammatory cells. The expression of IL-8 and VEGF was significantly correlated with MVD. The expression of IL-8 was also correlated with VEGF.2. 30 cases of fresh human brain gliomas, including 10 cases of diffuse astrocytoma (WHO grade II), 10 cases of anaplastic astrocytoma (WHO grade III) and 10 cases of glioblastoma (WHO grade IV), were used for frozen sections and were double stained for CD34, CXCR4 and SDF-1 with indirect immunofluorescence. It was observed that the average fluorescence intensities of CXCR4 and SDF-1 were increased with the tumor grades. The fluorescence intensity of grades III and IV were significantly stronger than grade II. The co-expression of SDF-1 and CXCR4 could be identified in vascular endothelial cells and tumor cells.In summary, the expression of IL-8, SDF-1 and its receptor CXCR4 were highty expressed in human astrocytic tumors and related to malignancy and angiogenesis of the tumor.