Expression of Timp-1, Timp-2, 72-Kda and 92-Kda Type-Iv Collagenase Transcripts in Human Astrocytoma Cell-Lines - Correlation With Astrocytoma Cell Invasiveness

Jt, Rutka; Matsuzawa, Kazuhito; Sl, Hubbard; Fukuyama, Kouzou; Le, Becker; Stetler‐Stevenson, W. G.; Edwards,; Pb, Dirks

doi:10.3892/ijo.6.4.877

Cited by 34 publications

(31 citation statements)

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“…Also, TIMP-2 expression does not change with glioma grade (Lampert et al, 1998) though again there is not universal agreement (Mohanam et al, 1995;Saxena et al, 1995). While it may not be relevant in vivo (Rutka et al, 1995) found no correlation between TIMP-1 and -2 expression and glioma cell invasiveness in vitro. As in the Lampert et al (1998) study, we found that TIMP-3 expression did not vary with glioma grade; however, one group found reduced expression by gene silencing via methylation (Bachman et al, 1999).…”

Section: Discussionmentioning

confidence: 85%

Differential expression and localization of TIMP-1 and TIMP-4 in human gliomas

Groft¹,

Muzik²,

Rewcastle

et al. 2001

Br J Cancer

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Studies have suggested that an imbalance of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) may contribute to the malignant phenotype of gliomas. In this study, we have undertaken a detailed analysis of expression of the TIMP family in normal human brain and malignant gliomas at both the mRNA and protein level. Reverse transcription-PCR (RT-PCR) analyses of total RNA from surgical tumour specimens revealed unique expression patterns for the 4 members of the TIMP family, with TIMP-1 and -4 showing positive and negative correlations, respectively, with glioma malignancy. By RT-PCR, TIMP-2 and TIMP-3 expression did not change with tumour grade. In situ hybridization localized TIMP-1 to glial tumour cells and also to the surrounding tumour vasculature. TIMP-4 transcripts were predominantly localized to tumour cells, though minor expression was found in vessels. Recombinant TIMP-4 reduced invasion of U251 glioma cells through Matrigel, and U87 clones overexpressing TIMP-4 showed reduced invasive capacity in vitro. TIMP-4, but not TIMP-1, blocked Membrane Type-1-MMP-mediated progelatinase-A (MMP-2) activation in human umbilical vein endothelial cells. The differential expression and localization of individual TIMPs may contribute to the pathophysiology of human malignant gliomas, particularly with regard to tumour vascularization. © 2001 Cancer Research Campaign http://www.bjcancer.com

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Section: Discussionmentioning

confidence: 85%

Differential expression and localization of TIMP-1 and TIMP-4 in human gliomas

Groft¹,

Muzik²,

Rewcastle

et al. 2001

Br J Cancer

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“…3 MMP-1 has been less well characterized in human brain tumors than other MMPs such as MMP-2 and MMP-9. [6][7][8][9][10][11] This may be due preconceptions that a collagenase would not be expected to play a prominent role in human brain tumors due to the absence of significant quantities of collagen I in the brain. Nevertheless, MMP-1 has in fact been shown to be present in these tumors.…”

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confidence: 99%

Association of a single nucleotide polymorphism in the matrix metalloproteinase‐1 promoter with glioblastoma

McCready

Broaddus

Sykes

et al. 2005

Intl Journal of Cancer

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A key feature in the malignant behavior of glioblastoma is the tendency to invade host brain tissue surrounding the primary tumor site. Several members of the matrix metalloproteinase family are thought to contribute to this invasive capacity. A single nucleotide polymorphism has been described in the matrix metalloproteinase-1 (MMP-1) promoter that consists of either the presence or absence of a guanine nucleotide at position 21607. The presence of the guanine base creates a functional binding site for members of the ETS family of transcription factors and has been shown to increase MMP-1 transcription. The purpose of our study was to characterize this polymorphism in human glioblastoma. Promoter genotyping was performed on brain tumor tissue obtained from 81 patients and compared to 57 healthy individuals. The 2G/2G genotype is more prevalent in glioblastoma tissue compared to healthy individuals (p 5 0.01). mRNA and protein expression were measured in a subset of brain tumor and normal brain tissue samples. MMP-1 protein levels are significantly higher in glioblastoma tissue compared to normal brain (p 5 0.001). Electromobility shift assays and promoter assays were performed to assess binding capability and transcriptional activity, respectively. Proteins present in glioma cell lines can specifically bind the 2G promoter probe. MMP-1 transcription is significantly higher in cells transfected with the 2G promoter when compared to cells transfected with the 1G promoter (p<0.02). This polymorphism may provide a mechanism for increased expression of MMP-1 in malignant gliomas via elevation of MMP-1 mRNA transcription and may underlie the invasive phenotype. ' 2005 Wiley-Liss, Inc.Key words: brain tumors; matrix metalloproteinases; transcriptional regulation; SNP Gliomas account for 44% of all primary central nervous system tumors and of these the most common is the highly malignant glioblastoma multiforme (GBM). 1 Despite significant improvements in the diagnosis and treatment for patients with a GBM, this primary brain tumor remains essentially incurable. Although surgery and radiotherapy substantially improve patient survival, 2 95% of patients have a mean survival of 2 years following diagnosis. Patients foregoing treatment have a mean survival time of 4 months. The characteristic ability of GBMs to invade surrounding normal tissue makes total surgical resection virtually impossible.Matrix metalloproteinase-1 (MMP-1), also known as collagenase-1, is a member of the MMP family of zinc-dependent endopeptidases, which have the ability to cleave substrates in the extracellular matrix. Substrates for MMP-1 include collagen types I, II, III, VII and X, gelatin, entactin, aggrecan and tenascin. Until recently it was thought that MMPs were responsible mainly for the degradation of extracellular matrix components. However it has become clear that the MMP family has a wide range of other influences on biologic processes including the generation of bioactive proteins. [3][4][5] Examples include the cleavage of the proteo...

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“…Invasive glioma cells migrate beyond the main tumor mass and render these surgically incurable (Kelly et al, 1987). Gelatinase-A or gelatinase-B are commonly overexpressed in glioma cell lines and surgical specimens (Forsyth et al, 1998(Forsyth et al, , 1999Nakagawa et al, 1996;Nakano et al, 1995;Rao et al, 1993Rao et al, , 1996Rutka et al, 1995;Sawaya et al, 1996;Uhm et al, 1996), but their precise function in gliomas is unknown. An understanding of their mRNA and protein localization in gliomas would help determine their functions in vivo and allow for rational targeting of MMP inhibition as a novel glioma treatment.…”

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confidence: 99%

Localization of gelatinase-A and gelatinase-B mRNA and protein in human gliomas

Raithatha¹

2000

Neuro-Oncology

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Malignant gliomas maintain a poor prognosis and survival rate due to their marked local invasive growth and neovascularization. Matrix metalloproteinases (MMPs) have been implicated in glioma invasion and angiogenesis, but it is unknown whether they are produced by the tumor cells or surrounding stroma. Using in situ hybridization and immunohistochemistry, we found expression of mRNA for both gelatinase-A (MMP2) and gelatinase-B (MMP9) localized to tumor cells and vascular structures in glioma sections. Gelatinase-A protein expression was detected most prominently in tumor cells, with very little signal seen in vasculature. Gelatinase-B protein expression was prominent in vascular structures but was also expressed in tumor cells. Our data show that these proteases are produced by glioma cells and vascular structures and suggest that synthetic MMP inhibitors might be useful in this disease.

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Expression of Timp-1, Timp-2, 72-Kda and 92-Kda Type-Iv Collagenase Transcripts in Human Astrocytoma Cell-Lines - Correlation With Astrocytoma Cell Invasiveness

Cited by 34 publications

References 0 publications

Differential expression and localization of TIMP-1 and TIMP-4 in human gliomas

Differential expression and localization of TIMP-1 and TIMP-4 in human gliomas

Association of a single nucleotide polymorphism in the matrix metalloproteinase‐1 promoter with glioblastoma

Localization of gelatinase-A and gelatinase-B mRNA and protein in human gliomas

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