Immunohistochemical analysis of reactive astrocytes around glioblastoma: an immunohistochemical study of postmortem glioblastoma cases
Introduction
Tumor cell invasion requires proteolytic degradation of extracellular matrices and neovascularization in the peripheral area adjacent to the tumor [1], [2]. Plasminogen activators and proteins of the matrix metalloproteinase (MMP) family are the major proteases that degrade peritumoral extracellular matrices. Vascular endothelial growth factor (VEGF) is a protein important for vascular proliferation within the tumor.
MMPS have been implicated in proteolytic degradation processes. Secretion of MMPs by tumor cells has been demonstrated in malignant brain tumors, and reportedly is associated with malignant progression of these neoplasms [3]. Reportedly, malignant gliomas express MMP-1, MMP-2, MMP-9 and TTMP-1 [4], [5]. In addition, vascular endothelial growth factor (VEGF) is normally active in embryogenesis and wound healing, and also is important in the growth of various tumors, including glioblastoma [6], [7], [8], [9], [10], [11].
On the other hand, proteolytic degradation and neovascularization outside of the tumor must occur not only in association with the tumor cell invasion, but also to facilitate tissue reconstruction processes that guard against the tumor cell invasion.
In this study, which entails immunohistochemistry on seven autopsy brain specimens with glioblastoma, we investigated the roles of MMPs, and VEGF in glioma cell invasion to the adjacent structures, and anti-tumor responses of adjacent brain tissues using graphic analysis.
Section snippets
Tissue preparation
Seven autopsy brain specimens from patients who died of glioblastoma, including four males and three females, were used for this study. The average age at diagnosis was 67.3 years. Patient's ages were in a range from 26 to 86 years old and the survival period after diagnosis was 480±502.7 days (mean±S.D.). Six patients were treated with surgical interventions followed by radiotherapy (average, 55 Gy) and intravenous infusion of 1-(4-amino-2-methyl-5-pyrimidinyl)
Results
Fig. 1 shows the result of MRI T1-Gd, where the patient was examined 1 month prior to death. Ki-67 and VEGF immunopositivity are also shown color graphically in a slice of whole brain. As demonstrated here, Ki-67 positive cells are mainly localized in the tumor, however, VEGF immunopositivity was stronger outside the tumor than in the tumor itself. This phenomenon strongly suggests that there is a natural tissue reaction against the tumor.
Fig. 2 demonstrates the immunopositivity of each protein
Discussion
The mechanisms by which glioma cells migrate and invade adjacent normal brain tissue are still under investigation, but cell-matrix proteolysis and neovascularization are necessary elements. In these processes, MMPs have proven to be key enzymes for glioma invasion. Among the 11 known MMPs, MMP-2 and -9 have been found to be associated with tumor cell invasion. The activated forms of MMP such as MT-MMP are necessary for proteolytic activity, and MMP function is influenced by antiproteolytic
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