| Gliomas are the most common primary neuroepithelium malignant tumor of central nervous system and a major unsolved public health problem,acount for 44.69 of all brain tumor. Despite optimal treatment with surgery, radiotherapy and chemotherapy, tumor recurrences are frequent and patients with gliomas continue to have poor prognoses. the most malignant glioma, is associated with an average life expectancy of only 12 months from diagnosis to death. The poor prognosis is partially because of the inability to deliver chemotherapeutic agents across the blood-brain barrier (BBB) and the low tumor response to radiation. partially include rapid glioma cell proliferation, resistance against apoptosis, distant invasion of the surrounding brain and high levels of angiogenesis. A major barrier to effective malignant glioma treatment is the invasion of these cells into brain parenchyma. Current treatment modalities are unable to significantly prolong survival in patients diagnosed with malignant glioma. as well as novel molecularly targeted therapies, glioma mortality and morbidity remain very high. Therefore, the poor treatment methods and prognosis for patients with glioma is a big trouble in the world. it is necessary to look for new treatment in order to improve prognosis and quality of patients with gliomas.Human and experimental gliomas express a number of receptor tyrosine kinases (RTKs) and corresponding ligands that contribute to their malignancy by enhancing glioma cell mitogenicity and motogenicity, inhibiting apoptosis and stimulating angiogenesis. These RTKs include the EGF receptor (EGFR), the HGF receptor c-Met, the PDGF receptor (PDGFR) and the VEGF receptor (VEGFR) and so on. Loss of tumor-suppressor function in high-grade gliomas also significantly contributes to their malignancy. Eph receptor tyrosine kinases (RTK) comprise the largest family of tyrosine kinases encoded in the human genome. sixteen Eph receptors and nine ephrin ligands have been identified to date and these molecules are increasingly understood to play important roles in disease and development. EphA2 is a first member of A-type of Eph subfamily which have RTK activity, it is over-expressed in different types of cancer including pancreatic, lung, melanoma, colorectal, ovarian, and breast. EphA2 played an important part in embryonic development by signal transduction, especially in nervous and blood-vascular system, it can regulate the cell multiplication,differentiation, and maintain the cell to adhere, promote the vascular to hyperplasy. When the EphA2 was abnormally expressed, it can induce the tumor to take place,angiogenesis,invasion,infiltration and diversion. EphA2 is over-expressed in gliomas and the overexpression of EphA2 is related to histological grade.Matrix metalloproteinase (MMPs ) are a family of zinc-dependent endopeptidases which play an active role in regulating the extracellular matrix (ECM). MMP family of enzymes consists of 25 endopeptidases in mice and 24 in humans. They are grouped into collagenases, gelatinases, stromelysins, matrilysins, membrane-type (MT)-MMPs and others and this grouping is based on domain organization and substrate preference . The MMP family plays an important role in the degradation of extracellular matrix in various physiological and pathological conditions. many disease processes show specific patterns of MMP expression, such as cancer, cardiovascular disease and arthritis. Accumulated evidence has suggested that MMPs contribute to cancer cell invasion of the surrounding normal tissues and metastasis through the cell-surface ECM degradation strong correlations have been reported between elevated MMP levels and tumor cell invasiveness in human gliomas. Among them, attention has been focused on gelatinases (MMP-2 and MMP-9) and membrane type MMPs (MT-MMPs). MMP-2 expression, but not MMP-9 expression, may be associated with invasion in gliomas. The current research showed that EphA2 overexpression induces a FAK-dependent increase in MMP2 expression and invasiveness. Although they two overexpressed in glioma tissues, the relationship of EphA2 and MMP2 is unknown now. In this study, we examine the expression and relationship of EphA2 and MMP2 in gliomas. The aim is to reveal the invasiveness of EphA2 in gliomas.ObjectiveTo investigate the expression and relationship of EphA2 and MMP2 in gliomas. MethodsTake 69 patients'glioma tissue as research objects, and 10 normal patients'brain tissues as control group. The positive rates of EphA2 and MMP2 in Glioma and normal brain tissue were detected using immunohistochemistry.Results1. The positive rate of EphA2 in 69 cases of glioma tissues and 10 cases of normal brain tissues was 69.6%(48/69) and 10%(1/10) respectively, the expression of EphA2 in glioma was obviously higher then normal brain tissue(p<0.01); the positive rate of EphA2 in low-grade gliomas (WHOⅠ~Ⅱ) and high-grade gliomas(WHOⅢ~Ⅳ) was respectively 37.0%(10/27) and 90.5%(38/42), the expression of EphA2 in high-grade gliomas was obviously higher then low-grade gliomas(p<0.01).2. The expression of EphA2 in gliomas had no relationship with patients'sex , age and position, size of gliomas.3. The positive rate of MMP2 in 69 cases of glioma tissues and 10 cases of normal brain tissues was 47.8%(33/69) and 0%(0/10) respectively, the expression of MMP2 in glioma was obviously higher then normal brain tissue(p=0.01); the positive rate of EphA2 in low-grade gliomas (WHOⅠ~Ⅱ) and high-grade gliomas(WHOⅢ~Ⅳ) was respectively 14.8%(4/27) and69.0%(29/42), the expression of MMP2 in high-grade gliomas was obviously higher then low-grade gliomas(p<0.01).4. The expression of MMP2 in gliomas had no relationship with patients'sex , age and position, size of gliomas.5. In the same glioma tissues, the expression of EphA2 was positive correlated with that of MMP2( r=0.660,P﹤0.01).Conclusions1. EphA2 and MMP2 are both overexpressed in glioma tissues simultaneously. The expression of them had a closely relationship with pathological grade of gliomas.2. The expression of EphA2 and MMP2 in gliomas had no relationship with patients'sex , age and position, size of gliomas.3. In the same glioma tissues, the expression of EphA2 was positive correlated with that of MMP2. EphA2 may enhance the invasion and metastasis of gliomas through MMP2. |
PDF Full Text Request