Membrane-Type I Matrix Metalloproteinase-Dependent Regulation of Rheumatoid Arthritis Synoviocyte Function

Sabeh, Farideh; Fox, David A.; Weiss, Stephen J.

doi:10.4049/jimmunol.0904068

Cited by 93 publications

(54 citation statements)

References 70 publications

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“…MT1-MMP promotes cancer cell invasion (1) and enables tumor stromal cells to help cancer cell growth (49), angiogenesis (50), invasion of inflammatory cells (51), and cartilage degradation by synovial pannus (6,52). It is important to inhibit MT1-MMP in a specific manner, but small molecular weight inhibitors targeting the active site of the enzyme are difficult to make specific because 62 human metalloproteinases share similar topology of their active sites.…”

Section: Discussionmentioning

confidence: 99%

MT-LOOP-dependent Localization of Membrane Type I Matrix Metalloproteinase (MT1-MMP) to the Cell Adhesion Complexes Promotes Cancer Cell Invasion

Woskowicz

Weaver

Shitomi

et al. 2013

Journal of Biological Chemistry

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Background: MT1-MMP promotes cancer cell invasion. Results: Deletion of the MT-LOOP region of MT1-MMP or an antibody to the MT-LOOP inhibits cellular invasion. Conclusion: MT-LOOP-dependent MT1-MMP localization to the cell adhesion complex promotes cellular invasion. Significance: Our work reveals a novel mechanism of MT1-MMP regulation during cellular invasion and identifies the MT-LOOP as a novel target region to develop specific inhibitors.

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Section: Discussionmentioning

confidence: 99%

MT-LOOP-dependent Localization of Membrane Type I Matrix Metalloproteinase (MT1-MMP) to the Cell Adhesion Complexes Promotes Cancer Cell Invasion

Woskowicz

Weaver

Shitomi

et al. 2013

Journal of Biological Chemistry

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“…MMP-14 appears to be the predominant MMP expressed by FLSs to degrade the collagenous cartilage matrix. 70 Other matrix enzymes (e.g., ADAMTS 5) degrade aggrecan and thus further diminish cartilage integrity.…”

Section: Cartilage Damagementioning

confidence: 99%

The Pathogenesis of Rheumatoid Arthritis

2011

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“…MT1-MMP is also an essential pericellular collagenase for cancer cells to grow in a collagen-rich environment (Hotary et al, 2003). MT1-MMP also plays a major role in angiogenesis (Chun et al, 2004; Hiraoka et al, 1998), in migration of smooth muscle cells to the neo-intima of the artery upon injury (Filippov et al, 2005) and in cartilage invasion by rheumatoid synovial tissue (Miller et al, 2009; Sabeh et al, 2010). Thus, MT1-MMP plays important roles in invasive processes of different cell types.…”

Section: Introductionmentioning

confidence: 99%

Basal localization of MT1-MMP is essential for epithelial cell morphogenesis in 3D collagen matrix

Weaver

Wolters

Ito

et al. 2014

Journal of Cell Science

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The membrane-anchored collagenase membrane type 1 matrix metalloprotease (MT1-MMP) has been shown to play an essential role during epithelial tubulogenesis in 3D collagen matrices; however, its regulation during tubulogenesis is not understood. Here, we report that degradation of collagen in polarized epithelial cells is post-translationally regulated by changing the localization of MT1-MMP from the apical to the basal surface. MT1-MMP predominantly localizes at the apical surface in inert polarized epithelial cells, whereas treatment with HGF induced basal localization of MT1-MMP followed by collagen degradation. The basal localization of MT1-MMP requires the ectodomains of the enzyme because deletion of the MT-loop region or the hemopexin domain inhibited basal localization of the enzyme. TGFβ is a well-known inhibitor of tubulogenesis and our data indicate that its mechanism of inhibition is, at least in part, due to inhibition of MT1-MMP localization to the basal surface. Interestingly, however, the effect of TGFβ was found to be bi-phasic: at high doses it effectively inhibited basal localization of MT1-MMP, whereas at lower doses tubulogenesis and basal localization of MT1-MMP was promoted. Taken together, these data indicate that basal localization of MT1-MMP is a key factor promoting the degradation of extracellular matrix by polarized epithelial cells, and that this is an essential part of epithelial morphogenesis in 3D collagen.

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Membrane-Type I Matrix Metalloproteinase-Dependent Regulation of Rheumatoid Arthritis Synoviocyte Function

Abstract: Material

Cited by 93 publications

References 70 publications

MT-LOOP-dependent Localization of Membrane Type I Matrix Metalloproteinase (MT1-MMP) to the Cell Adhesion Complexes Promotes Cancer Cell Invasion

MT-LOOP-dependent Localization of Membrane Type I Matrix Metalloproteinase (MT1-MMP) to the Cell Adhesion Complexes Promotes Cancer Cell Invasion

The Pathogenesis of Rheumatoid Arthritis

Basal localization of MT1-MMP is essential for epithelial cell morphogenesis in 3D collagen matrix

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