The Expression Of Tisse Factor In Gioma And Its Role In Angiogenesis

Tissue factor (TF) is an integral membrane glycoprotein 47 kD in size that, when assembled with factor VIIa (FVIIa), initiates coagulation. The TF-FVIIa complex is the main initiator of the coagulation cascade via activation of factor IX and X, thereby resulting thrombin production. Tissue factor is expressed on the surface of various cells including endothelial cells, fibroblasts, monocytes, and monocytelike cell lines. TF consists of a 263 amino acids organized into 219-amin-acid extracellular domain, 23-amino-acid transmembrane domain and 21-amino-acid cytoplasmic tail. The molecular structure of TF indicates that it may be classified in the class 2 cytokine receptor family, which include the receptors of interferon-(, -( and -(. However, apart from its well-known role in hemostasis, TF is also involved in a variety of cellular processes, including intracellular signaling, cellular proliferation, and the development of blood vessels, especially in tumor angiogenesis and metastasis. Knockout of the TF gene in a mouse model is associated with the death of the embryo between days 8.5 and 10.5 as the walls of yolk sac vessels fail to develop, implying a role for TF in normal fetal angiogenesis.Under some pathologic conditions, the strict regulation of TF expression is lost and constitutive expression abounds. For example may tumor cells, including those from patients with leukemias, express high levels of TF offering a major mechanism for the hypercoagulability associated with malignancy. Direct correlation between elevated TF expression and advanced stages of malignancy has been confirmed in several different types of cancers, including breast cancer, colorectal cancer, pancreatic cancer, and glioma. Since the 1970's when Folkman first demonstrated that solid tumors were dependent on angiogenesis to grow beyond a few millimeters, great steps have been taken to determine the factors involved in these processes. Various angiogenic activators and inhibitors have been characterized for their roles in angiogenesis. TF appears to augment this balance. Enforced expression of TF in sarcoma cells in mice promotes angiogenesis through the increased production of the positive angiogenic factor VEGF and reduced production of the negative angiogenic factor thrombospondin 2. Characterization of a number of human breast and melanoma cells demonstrated a strong correlation between TF and VEGF levels in tissue culture. In situ analysis of human lung and breast cancer specimens identified the co-localizationof there two factors. When high TF- and VEGF-producing melanoma cells were inoculated into immunodeficient mice, highly vascular tumors grew in vivo. In contrast, inoculation with low TF- and VEGF-producing melanoma cells produced relatively avascular tumors. In a mouse model of experimental melanoma metastasis, endogenous tumor cell TF expression correlates with metastatic potential, while transfection and overexpression of the TF gene enhances metastasis.Although many reports were used to describe the relationship between the TF and tumor, even some scholars regarded its as a tumor marker like PSA or CEA, until now we don't know what is the effect of TF on the tumor cells proliferation and if TF promote the angiogenesis by regulating the expression of VEGF and what is the effect of TF on other angiogenesis factors?Gliomas in the form of astrocytomas, anaplastic astrocytomas, and glioblastomas, which account for one-third of primary brain tumors, are typically characterized by rapid cell proliferation and a marked propensity to invade and damage surrounding tissues, and are among the most vascularized tumors. Tumor angiogenesis is correlated with metastasis and is a predictor of cancer-specific survival. Thus, neovascularization is likely to be an important step in the transition of a glioma from a latent state to a metastatic state that is associated with a poor prognosis. It still remain unclear that what is the effect of TF on the glioma progression and angiogenesis, in this report we evaluated the exp...