Gelatinolytic activity of matrix metalloproteinase‐2 and matrix metalloproteinase‐9 in rat brain after implantation of 9L rat glioma cells

Abstract

The matrix metalloproteinases (MMPs) have come to be highlighted by their close relation to the cell invasion of gliomas. The inhibitors of MMPs have undergone extensive development because of its effectiveness against tumor invasion and angiogenesis. Therefore, a suitable animal model is necessary for searching new MMPs inhibitors against gliomas. In this study, we established an experimental model by implanting 9L glioma cells stereotactically into Fisher344 (F344) rat's brain, and the expression and enzymatic activity of MMP-2 and MMP-9 in 9L glioma cells and in tumor tissue was determined by means of reverse transcription polymerase chain reaction (RT-PCR), sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) zymography, in situ film zymography and immunostaining. The results of RT-PCR showed that the mRNA level of MMP-2 in 9L glioma cells was higher than that of MMP-9, and the mRNA expression of MMP-9 was increased along with the growth of malignant gliomas. SDS-PAGE zymography revealed that the expression of MMP-2 and MMP-9 were significantly increased in tumor tissues, and the MMP-9 wasn't detected in normal tissue. The positive stain of MMP-2 and MMP-9 was enhanced with the growth of malignant gliomas, especially for MMP-9. The expression of active gelatinase was found in tumor tissue. In conclusion, the expression of active MMP-2 and MMP-9 was increased in 9L/F344 rat brain during the growth of malignant gliomas at different time intervals, which indicate that 9L/F344 animal model may be a prospective animal model to test new MMPs inhibitors.

Involvement of Akt/NF-κB pathway in antitumor effects of parthenolide on glioblastoma cells in vitro and in vivo

“…Aberrant MMP-9 expression is also implicated in the glioblastoma angiogenesis process. Low basal MMP-9 expression occurs in normal brain tissue, but high expression levels are induced in glioblastomas, and are linked to increased tumour cell proliferation [29]. We found that parthenolide suppresses both tumour cell-induced angiogenesis and expression of the NF-κB targets, i.e., VEGF and MMP-9, in glioblastoma cells.…”

Antitumor activities of synthetic and natural stilbenes through antiangiogenic action

“…(2) When MMPs are secreted from tumor cells, the invasion of tumor cells is facilitated by increased intravasation and extravasation through the degradation of the ECM and basement membranes. (3)(4)(5)(6) Zhao et al (7) reported that the expression of MMP-2 and MMP-9 was significantly increased in tumor tissue after implantation of 9L rat glioma cells. Moreover, the MMP proteolytic system may also modulate tumor angiogenesis by modulating the release of biologically active vascular endothelial growth factor (VEGF).…”

The Role of Matrix Metalloproteinases a nd Tissue Inhibitors of Metalloproteinases in the Progression of Astrocytomas

“…Among the MMPs that are commonly associated with the progression of astrocytic tumors are the gelatinases and the membrane MMPs, especially MT1-MMP1. Gelatinases A (MMP-2) and B (MMP-9) are undoubtedly the most well-studied MMPs in CNS tumors, and they have been identified as important factors in the development of high-grade gliomas (Munaut et al 2003;Pagenstecher et al 2001;Zhao, et al, 2007). This observation is directly linked to the invasive nature of these tumors because the expression levels of these gelatinases are generally low in normal brain tissue (Van Meter et al, 2001).…”