| Background Ovarian carcinoma has the highest mortalityrate among gynecological malignancies. Two thirds of patients with ovarian carcinoma present advanced-stage disease at the first diagnosis and have poor prognoses because of wide metastasis of cancer cells and rapidly accumulating ascetic fluid. Many agents have been confirmed to affect the pathogenesis and progression of ovarian cancer, including the disturbance of several factors and hormones. It is well acceptedthat the growth and metastasis of solid tumors are dependent on the formation of new blood vessels, a process called angiogenesis. Vascular endothelial growth factor (VEGF) is an important growth factor that can promote angiogenesis and vascular permeability. A lot of evidences suggest that VEGF is produced in elevated amounts by many tumors, including ovarian carcinomas. The level of VEGF is positive correlated with the tumor microvessel density and malignant degree. So the blockade of VEGF may be an efficient strategy to inhibit the formation of tumor angiogenesis and the growth of cancer. The known human VEGF receptors, Flt~l and KDR, are expressed predominantly on endothelial cells. In previous studies, it has been noted that VEGF receptors are also expressed on tumor cells, including ovarian cancer cells. Coexpression of VEGF and VEGFRs on the same tumor cell indicates that the autocrine stimulation of VEGF exists in tumor cell. Both of VEGFRs are cell surface tyrosine kinases and their signal functions are through Ins-P-i, PI3-kinase and MAP kinase pathway like other growth factor receptors. But recently, it has been found that JAK-STAT pathway also participates VEGF signaling.Signal transducers and activators of transcription (STATs) are a family of cytoplasmic proteins with roles as signal messengers and transcription factors that participate in normal cellular responses to cytokines and growth factors. Frequently,however, abnormal activity of certain STAT family members is associated with a wide variety of diseases, including human malignancies. Constitutive activations of STATs have been confirmed in many cancers, including ovarian cancer. Some studies evaluated constitutive Stat3 activation as a 'cancer-causing' factor. Agents causing aberrations in STAT signaling need advanced studies.In this study, we detected the expression levels of VEGFx VEGFRs proteins and the activated levels of STATs by immunohistochemical method (LSAB method) to determine the autocrine stimulation of VEGF existing in ovarian carcinoma and to clarify the roles of activated STATs in VEGF signaling. The study probably provided experimental evidences for a new target of anti-angiogenesis in tumor.Materials and Methods The tissue samples from 42 womenwith primary ovarian epithelial carcinoma (including 19 serous carcinomas, 10 mucinous carcinomas, 11 endometrioid carcinomas and 2 mixed carcinomas), 29 begnin ovarian tumors (including 11 serous cystadenomas, 16 mucinous cystadenomas and 2 mixed cystadenomas), and 11 normal ovarian tissues were obtained. A LSAB immunohistochemistry assay was usd to determine the expression of VEGF, VEGFRK VEGFR2, P-StatK P-Stat3^ P~Stat5> P-Stat6 proteins in those ovarian tissues, including cellular location and semi-quantitation. All the data were statisticallymanaged with SPSS 10. 0 for windows.Results 1> By immunohistochemistry, positive granules ofVEGF were located in the cytoplasm, while VEGFRs were located on the membrane and in the cytoplasm. Semi-quantitative score showed that the expression of VEGF protein in ovarian carcinomas was significantly higher than that in benign ovarian tumors and normal ovarian tissues (P<0. 001) . There also exists significant difference between benign tumors and normal ovarian tissues(P<0.05). Both VEGFR1 and VEGFR2 proteins were highly expressed in ovarian cancer tissue, including tumor cells and endothelial cells, while their expression levels in other ovarian tissues are significantly lower (P<0.001) . There was no significant difference between benign... |
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