The Expression Of CXCR4 And VEGF In Human Astrocytoma And Its Relationship With Angiogenesis

Backgrounds and ObjectivesAngiogenesis always exists with the development of many tumors from beginning to end, and is regarded as a sign of malignant progression of tumors. The increasements of angiogenesis in tumors not only meet the necessary oxygen and nutrients for the tumor cell growth, but also promote the proliferation and invasion of malignant tumor process.Many factors involve in this process.CXC chemokine receptor 4(CXCR4) belongs to the G protein-coupled receptor gene family. It is a kind of chemokine-mediated function in the exercise of GTP-connected dual transmembrane protein receptor. CXCR4 involved in the cell growth,development differentiation,apoptosis and other physiological function extensively,such as regulating the development of related T and B cells,inflammatory reaction,the forming of heart and vessels,the development of the central nervous system and so on.Many researchers have found that CXCR4 had a higher expression in many tumors.It may have a close relationship with the tumor's development,proliferation. metastasis and angiogenesis. CXCR4 plays a very important role in tumor angiogenesis especially. Vascular endothelial growth factor (VEGF) belongs to the vascular endothelial growth factor gene family. VEGF is the most important angiogenesis factor in tumor angiogenesis, and plays a key role in angiogenesis of a variety of malignant tumors.Some articles reported that CXCR4 and VEGF promoted breast tumor angiogenesis,but the mechanisms are unknown. Nowaday, CXCR4 expression in astrocytoma and the relationship with VEGF is rarely reported both at home and abroad.At the same time there are many arguments on the way CXCR4 regulating tumor angiogenesis. Therefore, to detect the expression of CXCR4 and VEGF mRNA and to explore their relation to clinical pathological grade and angiogenesis in human astrocytoma,it may be helpful to realize the clinical biological behavior and pathogenesis of astrocytoma,diagnosis,treatment and assess the prognosis of astrocytoma.Materials and MethodsWe have collected 43 cases of fresh astrocytoma in the second affilated hospital of Zhengzhou University from November 2008 to July 2009,inclulding 25 cases of male,18 of female. The mean age was 37.13±2.71.All cases were identified by two qualified pathologist, it was entirely astrocytoma. According to WHO (2007) Classifications of Astrocytoma, among all the 43 astrocytoma specimens, there were 11 WHO I,14 WHOⅡ,10 WHOⅢand 8 WHOⅣ. WHOⅠ～Ⅱlevels were consedered as the low grade while WHO III-IV levels as the high grade.11 cases of non-tumor brain tissues were saved for control group. When they were removed from the brain tissue, all samples were immediately frozen in deep freeze refrigerator which kept the temperature at -80℃until extraction for reverse transcription polymerase chain reaction(RT-PCR).Part of each specimen was stored for hematoxylin and ensin stain.The expression of CXCR4 and VEGF mRNA in 43 cases of astrocytoma and 11 cases non-tumor brain tissues were determined by RT-PCR, and semi-quantification of banddensities were also performed. The results were statistically analyzed by SPSS 11.0 software.Results were considered significant when a=0.05. Results1,The relative expression of CXCR4 mRNA and the positive rate in astrocytoma were higher than non-tumor brain tissues(0.73±0.15 and 0.13±0.01;72.1% and 9.1%),there was a significant difference between them(P<0.01).The relative expression of CXCR4 mRNA in gradeⅢ～Ⅳand gradeⅠ～Ⅱwas 0.89±0.05, 0.62±0.06 respectively,there was a significant difference between them(t=16.19,P <0.01).2,The expression of VEGF mRNA was negative or weak in non-tumor brain tissues.there was a significant difference between the non-tumor brain tissues and the tumor groups(t=33.80,P<0.01).The relative expression of VEGF mRNA in gradeⅠ～Ⅱand gradeⅢ～Ⅳwas 0.72±0.05 and 0.97±0.04 respectively,there was a difference between them(P<0.01).3,There was a positive correlation between the expression of CXCR4 mRNA and the expression of VEGF mRNA in astrocytoma. In the positive expression groups of CXCR4 and the negative groups in astrocytoma, the positive expression rates of VEGF mRNA were 80.6%(25/31) and 33.3%(4/12) respectively,there was a moderate positive correlation between them(r=0.453,P=0.002).Conclusions1,The gene expression of CXCR4 and VEGF in astrocytoma is higher, and which increases with the development of histological grade. It suggests that they may take part in the proliferation and tumor invasion of astrocytoma. It may be useful to decide the prognostic of astrocytoma by investigating the two genes.2,There was a positive correlation between the expression of CXCR4 and the expression of VEGF. There might be some correlation between them because the two genes activate at the same time.CXCR4 probably takes part in the generation of astrocytoma' angiogenesis through increasing the secretion of VEGF.