The Expression And Significance Of Integrin β₃, MMP-2 And VEGF In Glioma

Background and objectiveThe most common malignant tumor in human central nervous system is glioma. It has taken many clinical difficulities and became the main reason of patients' death.It has been reported that invasion and metastasis of the malignant tumor take three -steps mechanism: 1. Tumor cell attaches to host cellular or extracellular matrix; 2. Proteolysis secreted by tumor cell degenerate local matrix; 3. Tumor cell protrudes pseudopod and makes movement to the degenerated basement membrane. Tumor cell breaks through the host barriers and induces the invasion and metastasis.Integrin is an important type of cell adhesion molecular. It plays an important role in the adhesion of cell and matrix, cell and cell, and the signal transduction. Integrin participates in the carcinogenesis and development of the tumor. There is a relation between the uncontrollable growth, poor differentiation, invasion, metastasis of the tumor and the expression, distribution in the cell surface of the integrin.Matrix metalloproteinases play important roles of in the invasion and metastasis of malignant tumors. MMP-2 belongs to gelatinase, and is an important type of matrix metalloproteinases. Vascular endothelial growth factor (VEGF, also known as vascular permeability factor, VPF) is a multifunctional cytokine, which can be expressed not only in normal developing cells and adult tissues but also in many types of tumor cells. Many oversea and domestic researches suggest that VEGF expression is closely associated with the grading, invasiveness, peritumor edema, prognosis, recurrence of tumor, and even microveesel density (MVD).In this experiment, the protein expressions of Integrinβ₃, MMP-2 and VEGF in 41 cases of brain glioma at every grade and the tumor-adjacent normal tissues were measured by immunohistochemistry for the purpose of understanding the expression regularity in gliomas. The effects of Integrinβ₃, MMP-2 and VEGF on the genesis, progression, invasion, and angiogenesis of glioma were also explored. The purpose of this study was to detect the expression of Integrinβ₃, MMP-2 and VEGF in human brain glioma. There is no report on the united detection of Integrinβ₃, MMP-2 and VEGF. And the united detection of Integrinβ₃, MMP-2 and VEGF may increase the diagnostic accuracy of the glioma and guide the clinical treatment.Materials and methods41cases of brain glioma were collected in the First Affiliated Hospital, Zhengzhou University. All the cases had no history of the chemotherapy, radiotherapy and immunotherapy. All cases were identified by pathologist. According to the WHO separating criteria about brain tumor in 1999, 22 cases were low potential malignancy, grade II ;19 cases were high potential malignancy, gradeIII.Also, there were 16 cases of tumor-adjacent normal brain tissue. The expression of Integrinβ₃, MMP-2 and VEGF protein were detected in 41 cases of brain glioma, and 16 cases of tumor-adjacent normal brain tissues by immunohistochemistry. All the data were analyzed by SPSS10.0 statistical package, the count information calculated the positive rate .The comparison of positive rate uses the Chi-square, the mean of more than two groups uses ANVOA. The relations of two variable are analyzed by Spearman's correlation analysis. The level of significant difference was a=0.05. Results1.The positive rates of expression of Integrinβ₃ protein in normal brain tissue, low potential malignancy and high potential malignancy brain glioma were 18.8%, 54.5%, and 84.2% respectively. There was a significant difference among them (P< 0.05) .2.The positive rates of expression of MMP-2 protein in normal brain tissue, low potential malignancy and high potential malignancy brain glioma were 25.0%, 59.1% and 89.5% respectively. There was a significant difference among them (P< 0.05) .3.The positive rates of expression of VEGF protein in normal brain tissue, low potential malignancy and high potential malignancy brain glioma were 18.8%, 50.0% and 89.5% respectively. There was a significant difference among them (P< 0.05) .4. There was a positive correlation between the positive expression rate of Integrinβ₃ protein and the expression rate of MMP-2 protein in human brain glioma. The positive expression rates of MMP-2 in positive expression group of Integrinβ₃ protein and negative group in human brain glioma were 89.3% (25/28) and 38.5% (5/13) respectively.5. There was a positive correlation between the positive expression rate of MMP-2 protein and the expression rate of VEGF protein in human brain glioma. The positive expression rates of VEGF in positive expression group of MMP-2 protein and negative group in human brain glioma were 86.7% (26/30) and 18.2% (2/11) respectively.6. There was a positive correlation between the positive expression rate of Integrinβ₃ protein and the expression rate of VEGF protein in human brain glioma. The positive expression rates of VEGF in positive expression group of Integrinβ₃ protein and negative group in human brain glioma were 85.7% (24/28) and 30.8% (4/13) respectively. Conclusions1. In different brain tissues, the rates of the expression of Integrinβ₃, MMP-2 and VEGF protein increased gradually from normal brain tissue to low potential malignancy and high potential malignancy brain glioma .It implied that the expression of Integrinβ₃, MMP-2 and VEGF protein correlated with the occurrence of the glioma.2. The expression of Integrin P 3, MMP-2 and VEGF has positive correlation to the glioma grading. It implied that the high expression of Integrinβ₃, MMP-2 and VEGF protein might make great contribution to cellular differenation and malignant progress.3. There was a positive correlation among the expression of Integrinβ₃, MMP-2 and VEGF protein. It implied that the expression of Integrinβ₃, MMP-2 and VEGF protein had the consistency. Integrinβ₃, MMP-2 and VEGF play cooperative roles in the occurrence and malignant development of the glioma.4. The united detection of Integrinβ₃, MMP-2 and VEGF may increase the diagnostic accuracy of the glioma and guide the clinical treatment.