Effect Of VEGF-C And Its Recepter FLT4 On Invasion Of Gliomas

IntroductionThe malignant tumor is the second death - related disease in the world, and a kind of disease of multi - stage in which many factors and genes participate. Nowadays, scienctists haven't yet find out the valid methods to cure tumors. The major prognostic factors are tumor's invasiveness and metastasis. The tumor transfers and encroaches upon is after it prepare the badly main factor. Gliomas is the most common intracranial malignant tumors. Compared with the non - central nervous tumors, gliomas is characteristic of local invasiveness of single cell and rare metastasis to extracranium via vascular or lymphamatic systems. Gliomas often impaired nerve function, resulting in increased intracranial pressure and following bad prognosis because of less intracranial compensatory capacity (10% ). Most of gliomas were hard to diagnosed clinically in early stage and difficult to be carried out radical resection therapy plus radiotherapy and/or chemotherapy while symptoms occur. How to control cancerous vascularization has become a major factor to prevent patients with gliomas from recurrence after radio - or chemo - therapy or surgical operation, and to increase five — years survial rate.VEGF - C and its receptor FLT4 have been currently detected to served as a set of regulator to regulate the lymphatic genesis and maturation of embryonic tissue. High expression of VEGF - C has been observed in many solid tumors, and correlated with tumor metastasis.It has not been reported what roles VEGF - C and FLT4 played in angio-gensis, invasiveness and metastasis of gliomas. Our study was to detect the expressions of VEGF - C and FLT4 in gliomas, and further to discuss their effectson angiogenesis, thereby providing theoretical basis for target therapy.Materials and Methods1. PatientsThirty cases of paraffin - embedded specimens of gliomas were derived from China Medical University from April to Oct of 2005, and pathologically diagnosed according to WHO glioma classification (1999yr). None of the patients had received radiotherapy or chemotherapy before operation. The median age was 37 years (range from 25-52).2. MethodAll of specimin were fixed by 4% Formaldehyde, paraffin - embedded, resected to 4jxm thickness. S - P immunohistochemistry {IHC) was used to detect the VEGF - C and FLT - 4 expression. Primary antibody: rabbit anti - human VEGF - C polyclonal antibody, 1:100 dilution( Boshide Biotechnology Company, Wuhan) and rabit anti -huaman polyclonal FLT -4 antibody, 1:100 dilution ( Boshide Biotechnology Company, Wuhan). PBS replaced primary antibody to served as negtive control. The ditailed procedure of IHC regered to product instruction.3. Statistical AnalysisSPSS11.0 software was employed to analyze all data. Statistical evaluation was performed using chi - square test, t - test. P <0.05 was considered as statistically significant.Results1. Expression of VEGF - C and FLT - 4 proteinVEGF - C protein were mainly located in cytoplasm of gliomas cells, presenting clearly brown staining particles, partially expressed in vascluar endotheli-al cell, and not lacated in normal intracranial tissues. VEGF - C protein expression was detected in 14/30 (46.7% ) gliomas. FLT -4 was mostly expressed in vascular endothelial cells and peripheral cytoplasm of gliomas cells.2. Correlation of VEGF - C and FLT -4 expression with pathological characteristicour results found there was no statistic correlation between VEGF - C andFLT -4 protein expression and patients'age, sex. However, VEGF - C and FLT-4 expression were positively correlated with malignant grade of gliomas. Withthe elevated malignant grade, VEGF - C, FLT -4 protein and positive FLT -4vessel counting were also increased.3. Relationship between VEGF - C and FLT -4Additionally, FIT -4 protein was detected in 9 of 14(64. 3 % ) gliomas with positively expressional VEGF - C. There was statistic correlation between protein expression of VEGF - C and FLT -4, r =0.4637 ,P =0.Oil.DiscussionThe malignant gliomas is abundant in pathological vessels. The clinical and animal experiment has confirmed the most common invasive pathway of gliomas was to infiltrate and spread via basement membrance. VEGF - C was expressed in many tumors. Its receptor, FLT -4 expression was time - specific,expressed in endothelial cell and at the phase of embryo, and then located in venous and lymphatic vessel. FIT - 4 protein was re - expressed in tumor vascular endothelial cells, which showed that VEGF - C regulated vessel and lymphatic formation of tumor stroma. Our study showed VEGF - C and FLT - 4 could be also expressed in gliomas. Additionally, FIT -4 protein was detected in 9 of 14(64. 3 % ) gliomas with positively expressional VEGF - C. There was statistic correlation between protein expression of VEGF - C and FLT - 4 ( r = 0. 4637, P < 0. 05. ), indicating that VEGF - C could up - regulate FLT -4.Moreover, our study showed that positive FLT - 4 vessels could be detected in all grade of gliomas. Positive FLT -4 vessel counting also increased with the increased VEGF - C expression, and expressed less in negative VEGF - C group. This result was similar to report of Tsurasali. Additionally, VEGF - C also expressed in vessel cells, and might enhance the permeability of vessel by regulating FLT - 4, and further promote endothelial cell migration, proliferationand tumor cell metastasis.On the whole, VEGF - C/FLT4 system is associated with lymphatic vessel formation, which we can utilize to block this signal pathway and inhibit tumor vessel formation, differentiation and growth, thus providing theoretical basis for target therapy of gliomas.Conclusion1. VEGF - C and its receptor FLT4 highly expressed in gliomas, thus promoting vessel formation and invasiveness.2. The expression of VEGF - C is positively correlated with FLT4.3. The expression of VEGF - C and FLT -4 is positively with malignant degree of gliomas.