Matrix Metalloproteinases Regulate Neovascularization by Acting as Pericellular Fibrinolysins

Hiraoka, Nobuaki; Allen, Edward; Apel, Ingrid J.; Gyetko, Margaret R.; Weiss, Stephen J.

doi:10.1016/s0092-8674(00)81768-7

Cited by 662 publications

(570 citation statements)

References 52 publications

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“…TIMP-4 overexpression in breast carcinoma cells resulted in less vascular tumours in vivo (Wang et al, 1997). Several pieces of evidence suggest that MT-MMPs are effectors of neovascularization, including the finding that MT1-MMP has been shown to act as a pericellular fibrinolysin and promote neovessel formation in vitro (Hiraoka et al, 1998). Moreover MT1-MMP-/-mice show profound growth abnormalities related to defects in vascularization of the growth plate during osteogenesis, and fail to induce vessel formation in corneal micropocket assays in response to bFGF (Zhou et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

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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: 99%

“…In particular, Gelatinase-A (MMP-2) and the MT-MMPs that activate it on the cell surface have been linked with both tumour cell invasion and angiogenesis Hiraoka et al, 1998;Belien et al, 1999;Forsyth et al, 1999;Llano et al, 1999;Nakada et al, 1999;Price et al, 1999;Raithatha et al, 2000).…”

mentioning

confidence: 99%

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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“…28,29 Disturbed angiogenesis has been noted in mice lacking MMP-2, -9 and MT1-MMP. 28,29,[73][74][75] Inhibition of angiogenesis has also been detected in in vivo studies by treatment of tumourbearing animals with MMP inhibitors. 76 Inhibition of angiogenesis in vivo has been shown at least with MMP inhibitors prinomastat, 76 BAY 12-9566, 77 batimastat, 78 BMS-275291, 79 neovastat 80 and metastat.…”

Section: Mmps and Tumour Angiogenesismentioning

confidence: 99%

Matrix metalloproteinases in cancer: Prognostic markers and therapeutic targets

Vihinen

Kähäri

2002

Intl Journal of Cancer

581

484

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Degradation of extracellular matrix is crucial for malignant tumour growth, invasion, metastasis and angiogenesis. Matrix metalloproteinases (MMPs) are a family of zinc-dependent neutral endopeptidases collectively capable of degrading essentially all matrix components. Elevated levels of distinct MMPs can be detected in tumour tissue or serum of patients with advanced cancer and their role as prognostic indicators in cancer is studied. In addition, therapeutic intervention of tumour growth and invasion based on inhibition of MMP activity is under intensive investigation and several MMP inhibitors are in clinical trials in cancer. In this review, we discuss the current view on the feasibility of MMPs as prognostic markers and as targets for therapeutic intervention in cancer.

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“…These findings are consistent with the observation that fibroblasts promoted tumor progression in animal models through their production of MMPs (Masson et al, 1998;Noel et al, 1993) and emphasize the importance of tumor-host interactions during cancer progression. MT1-MMP is also expressed by endothelial cells during migration (Galvez et al, 2001;Hiraoka et al, 1998).…”

Section: Mt1-mmp and Cancermentioning

confidence: 99%

Membrane type-1 matrix metalloproteinase and TIMP-2 in tumor angiogenesis

et al. 2003

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The matrix metalloproteinases (MMPs) constitute a multigene family of over 23 secreted and cell-surface associated enzymes that cleave or degrade various pericellular substrates. In addition to virtually all extracellular matrix (ECM) compounds, their targets include other proteinases, chemotactic molecules, latent growth factors, growth factor-binding proteins and cell surface molecules. The MMP activity is controlled by the physiological tissue inhibitors of MMPs (TIMPs). There is much evidence that MMPs and their inhibitors play a key role during extracellular remodeling in physiological situations and in cancer progression. They have other functions that promoting tumor invasion. Indeed, they regulate early stages of tumor progression such as tumor growth and angiogenesis. Membrane type MMPs (MT-MMPs) constitute a new subset of cell surface-associated MMPs. The present review will focus on MT1-MMP which plays a major role at least, in the ECM remodeling, directly by degrading several of its components, and indirectly by activating pro-MMP2. As our knowledge on the field of MT1-MMP biology has grown, the unforeseen complexities of this enzyme and its interaction with its inhibitor TIMP-2 have emerged, often revealing unexpected mechanisms of action.Keywords: MT1-MMP ; tumoral angiogenesis ; vascular endothelial growth factor ; protease inhibitors ; estradiol MMP structure and functionsMatrix metalloproteinases (MMPs) are a broad family of zinc-binding endopeptidases that play a key role in the extracellular matrix (ECM) degradation associated with cancer cell invasion, metastasis and angiogenesis (Egeblad and Werb, 2002;McCawley and Matrisian, 2000). At present, more than 21 human MMPs and the homologues from other species have been identified (Egeblad and Werb, 2002). The MMP family can be segregated into two groups, the soluble type and the membrane-type MMPs (MT-MMPs and MMP23). Although initially classified according to their substrate specificity (McCawley and Matrisian, 2000), the MMP classification is now based on their structure (Egeblad and Werb, 2002). The 'minimal-domain MMPs' (MMP7 and MMP26) contains (i) a signal peptide that directs them to the endoplasmic reticulum, (ii) a propeptide, with a zinc-interacting thiol (SH) group that maintains the proMMP in a latent form (zymogen), and (iii) a catalytic domain containing the highly conserved Zn 2+ binding site (HEXGHXXGXXHS/T) (Fig. 1). With the exception of MMP23, all other MMPs display a prolinerich hinge region that links the catalytic domain to the hemopexin/vitronectin-like domain. This C-terminal domain influences substrate specificity and the binding to tissue inhibitors of MMPs (TIMPs) and cell surface molecules. The hemopexin-containing MMPs are further distinguished by the presence of specific insert(s). The gelatin-binding MMPs (MMP2 and MMP9 or gelatinases) contain inserts that resemble the collagen-binding type II repeats of fibronectin. The membrane type (MT)-MMPs have a single pass transmembrane domain and a short cytoplasmic...

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Matrix Metalloproteinases Regulate Neovascularization by Acting as Pericellular Fibrinolysins

Cited by 662 publications

References 52 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

Matrix metalloproteinases in cancer: Prognostic markers and therapeutic targets

Membrane type-1 matrix metalloproteinase and TIMP-2 in tumor angiogenesis

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