Human glioma U‐251 cells contain type 1 plasminogen activator inhibitor in a rapidly releasable form

Salonen, Eeva‐Marjatta; Gombau, Lourdes; Engvall, Eva; Schleef, Raymond R.

doi:10.1016/0014-5793(96)00865-4

Cited by 4 publications

(4 citation statements)

References 30 publications

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“…MMP-2 has been shown to cleave native and denatured collagen type I (Aimes and Quigley, 1995). The basal levels of collagen degradation by Uneo cells were not affected by exogenous TIMP-2 even at the highest concentration used in this study apparently indicating the activity of TIMP-2-independent proteinases, for example of the uPA system found in U251 glioma (Rao et al, 1993;Salonen et al, 1996). This finding also demonstrates a lack of substantial contribution of other TIMP-2-sensitive MMPs which have been implicated in direct degradation of matrix proteins.…”

Section: Discussionmentioning

confidence: 48%

Matrix metalloproteinase-2 activation modulates glioma cell migration

Deryugina¹,

Bourdon²,

Luo³

et al. 1997

Journal of Cell Science

166

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Stable transfection of U251.3 glioma cells with cDNA encoding MT-MMP-1 resulted in increased cell surface expression of MT-MMP-1 and TIMP-2, constitutive activation of MMP-2 proenzyme and increased collagen degradation. In tumor spheroid outgrowth assays, cell migration of MT-MMP-1 transfectants relative to control was enhanced on collagen and decreased on vitronectin and fibronectin. These effects were reversed by TIMP-2 and were not associated with any substantial changes in cell adhesion. Binding of U251.3 cells to the C-terminal domain of MMP-2 was specifically inhibited by anti-(alpha)vss3 integrin blocking antibody indicating that MMP-2 interacts with (alpha)vss3 through the enzyme's C-terminal portion at or near the integrin's matrix adhesion sites. We propose that these mechanisms could govern directed matrix degradation in the tumor cells' microenvironment by sequestration of active MMP-2 on the cell surface. Our data suggest that activation of MMP-2 and its proteolytic activity localized to the cell surface could differentially modulate tumor cell migration in response to particular matrix proteins by altering both composition of the extracellular matrix and expression of adhesion receptors on the cell surface.

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Section: Discussionmentioning

confidence: 48%

Matrix metalloproteinase-2 activation modulates glioma cell migration

Deryugina¹,

Bourdon²,

Luo³

et al. 1997

Journal of Cell Science

166

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“…(20). Recent information from our group indicates that human glioma U-251 cells also contain PAI-1 in a rapidly releasable form (65), which raises the possibility that the proteins and mechanisms involved in the packaging of PAI-1 into storage granules may not be solely limited to megakaryocytes/platelets and the hemostatic system.…”

Section: Interaction Of Sgp-23 With Chromatographic Resins and Proteimentioning

confidence: 99%

Purification of Storage Granule Protein-23

Lang

Chuang

Barbas

et al. 1996

Journal of Biological Chemistry

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“…29 Several malignant tumors, including human malignant gliomas, have been shown to produce uPA. 10,14,30 Cells possess speci®c receptors for uPA providing an inducible, transient and localized cell surface proteolytic activity. Tumor invasiveness and metastasis can be blocked by a directed reduction of uPA activity.…”

Section: Introductionmentioning

confidence: 99%

“…Protease inhibitors are often co-expressed with the plasminogen activators, 19,20,30 and a high expression of plasminogen activator inhibitor-1 (PAI-1) is thought to be associated with the malignant progression of astrocytic tumors. 39 Recently PAI-1 has also been proposed as a new risk factor in head and neck cancer.…”

Section: Introductionmentioning

confidence: 99%

Expression of the proteolytic factors, tPA and uPA, PAI‐1 and VEGF during malignant glioma progression

Sandström

Johansson

Sandström

et al. 1999

Intl J of Devlp Neuroscience

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Various proteases and their inhibitors have been shown to be important in tumor invasion. Angiogenesis is further a prerequisite for the growth and progression of solid tumors. Since these systems are functionally linked, in situ hybridization and in situ zymography were used to investigate the spatial and temporal expression of factors representative of the plasmin/plasminogen system and of an angiogenic factor in the BT4C glioma model. This tumor is invasive with a high grade of neovascularization. Tissue-type plasminogen activator urokinase-type plasminogen activator and plasminogen activator inhibitor-1 mRNA were expressed in glioma cells during the entire tumor growth. Early in the tumor development the expression was found throughout the small tumor (approximately 10 mm3) while later in the time course the expression was found predominantly in the invasive tumor border of the tumor. The in situ zymography demonstrated that the plasminogen activators were translated into functional proteins. Vascular endothelial growth factor mRNA was expressed following a similar spatial and temporal pattern with an early expression in the entire small tumor while later, in larger tumors, it was exclusively expressed in the invasive tumor edge. In normal brain, the ventricular ependyma, meninges, as well as scattered neurons expressed tissue-type plasminogen activator mRNA. Vascular endothelial growth factor mRNA was observed in the choroid plexus, and in scattered cells in normal brain tissue. Our finding may suggest a functional co-operation of tissue-type plasminogen activator, urokinase-type plasminogen activator, plasminogen activator inhibitor-1 and vascular endothelial growth factor during glioma progression. This model could be of value when evaluating different treatment modalities aimed at blocking the migrating capacity and growth of glial tumors.

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Human glioma U‐251 cells contain type 1 plasminogen activator inhibitor in a rapidly releasable form

Cited by 4 publications

References 30 publications

Matrix metalloproteinase-2 activation modulates glioma cell migration

Matrix metalloproteinase-2 activation modulates glioma cell migration

Purification of Storage Granule Protein-23

Expression of the proteolytic factors, tPA and uPA, PAI‐1 and VEGF during malignant glioma progression

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