Matrix metalloproteinases 19 and 20 cleave aggrecan and cartilage oligomeric matrix protein (COMP)

Stracke, Jan Olaf; Fosang, Amanda J.; Mercuri, Francesco; Pendás, Alberto M.; Llano, Elena; Perris, Roberto; Cesare, Paul E. Di; Murphy, Gillian; Knäuper, Vera

doi:10.1016/s0014-5793(00)01819-6

Cited by 121 publications

(87 citation statements)

References 43 publications

(72 reference statements)

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“…Purified COMP has been reported to be digested by several matrix metalloproteinases (MMPs), including interstitial collagenase (MMP-1), collagenase-3 (MMP-13), stromelysin-1 (MMP-3), gelatinase-B (MMP-9), MMP-19, and enamelysin (MMP-20) (60). Recently, it was found that ADAMTS-4 can also cleave purified COMP in vitro (61); in this study, we present evidence showing that both the recombinant catalytic domain and intact ADAMTS-7 also digest COMP in vitro.…”

Section: Discussionmentioning

confidence: 99%

ADAMTS‐7: a metalloproteinase that directly binds to and degrades cartilage oligomeric matrix protein

Liu¹,

et al. 2006

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Degradative fragments of cartilage oligomeric matrix protein (COMP) have been observed in arthritic patients. The physiological enzyme(s) that degrade COMP, however, remain unknown. We performed a yeast two-hybrid screen (Y2H) to search for proteins that associate with COMP to identify an interaction partner that might degrade it. One screen using the epidermal growth factor (EGF) domain of COMP as bait led to the discovery of ADAMTS-7. Rat ADAMTS-7 is composed of 1595 amino acids, and this protein exhibits higher expression in the musculoskeletal tissues. COMP binds directly to ADAMTS-7 in vitro and in native articular cartilage. ADAMTS-7 selectively interacts with the EGF repeat domain but not with the other three functional domains of COMP, whereas the four C-terminal TSP motifs of ADAMTS-7 are required and sufficient for association with COMP. The recombinant catalytic domain and intact ADAMTS-7 are capable of digesting COMP in vitro. The enzymatic activity of ADAMTS-7 requires the presence of Zn 2+ and appropriate pH (7.5-9.5), and the concentration of ADAMTS-7 in cartilage and synovium of patients with rheumatoid arthritis is significantly increased as compared to normal cartilage and synovium. ADAMTS-7 is the first metalloproteinase found to bind directly to and degrade COMP.-Liu, C., Kong, W., Ilalov, K., Yu, S., Xu, K., Prazak, L., Fajardo, M., Sehgal, B., Di Cesare, P. E. ADAMTS-7: a metalloproteinase that directly binds to and degrades cartilage oligomeric matrix protein. The extracellular matrix (ECM) of cartilage consists of several types of collagens, proteoglycans, and other noncollagenous macromolecules, all of which interact to form a highly specialized connective tissue (1). Early extracellular cartilage matrix degeneration in arthritis is the result of the action of degradative enzymes. As the severity of arthritis progresses, the synthesis and secretion of matrix-degrading enzymes markedly increase (2). The control 1 These authors contributed equally to this work.

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Section: Discussionmentioning

confidence: 99%

ADAMTS‐7: a metalloproteinase that directly binds to and degrades cartilage oligomeric matrix protein

Liu¹,

et al. 2006

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“…6 The catalytic domain of MMP19 degrades various ECM components including collagen type IV, nidogen-1, fibronectin, tenascin-C isoform, aggrecan, and laminin-5-gamma-2-chain. [7][8][9] The catalytic domain contains the typical zinc-binding motif; the zinc and calcium ions additional to this domain are necessary for structure stability and enzymatic activities of MMPs. 10 The glutamate residue at the zinc binding motif activates the zinc-bound water molecule to provide the nucleophile during cleaving activities on peptide bonds.…”

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Catalytic activity of matrix metalloproteinase‐19 is essential for tumor suppressor and anti‐angiogenic activities in nasopharyngeal carcinoma

Chan

Lung

et al. 2011

Intl Journal of Cancer

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The association of Matrix metalloproteinase-19 (MMP19) in the development of nasopharyngeal carcinoma (NPC) was identified from differential gene profiling, which showed MMP19 was one of the candidate genes down-regulated in the NPC cell lines. In this study, quantitative RT-PCR and Western blot analysis showed MMP19 was down-regulated in all seven NPC cell lines. By tissue microarray immunohistochemical staining, MMP19 appears down-regulated in 69.7% of primary NPC specimens. Allelic deletion and promoter hypermethylation contribute to MMP19 down-regulation. We also clearly demonstrate that the catalytic activity of MMP19 plays an important role in antitumor and antiangiogenesis activities in comparative studies of the wild-type and the catalytically inactive mutant MMP19. In the in vivo tumorigenicity assay, only the wild-type (WT), but not mutant, MMP19 transfectants suppress tumor formation in nude mice. In the in vitro colony formation assay, WT MMP19 dramatically reduces colony-forming ability of NPC cell lines, when compared to the inactive mutant. In the tube formation assay of human umbilical vein endothelial cells and human microvascular endothelial cells (HMEC-1), secreted WT MMP19, but not mutant MMP19, induces reduction of tube-forming ability in endothelial cells with decreased vascular endothelial growth factor (VEGF) in conditioned media detected by enzyme-linked immunosorbent assay (ELISA). The anti-angiogenic activity of WT MMP19 is correlated with suppression of tumor formation. These results now clearly show that catalytic activity of MMP19 is essential for its tumor suppressive and anti-angiogenic functions in NPC.Nasopharyngeal carcinoma (NPC) is a malignancy arising from the epithelial cells of the nasopharynx. This cancer has a unique racial and geographic distribution with a high incidence in Southern China and Southeast Asia among the Southern Chinese population. 1 The etiology of NPC is believed to be multifactorial including dietary and

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“…[26][27][28] MMP19 is able to cleave several components of the extracellular matrix such as collagen IV, nidogen, tenascin C, laminin 5g2, fibronectin, cartilage oligomeric protein, aggrecan, and secreted insulin-like growth factor binding protein 3, thus modulating IGF signaling pathway. 25,[29][30][31][32] In this study, we evaluated the expression of MMP19 in cutaneous melanoma at different stages of progression using immunohistochemistry. We found that the expression of MMP19 increases during the melanoma progression and that MMP19 activity facilitates the migration of tumour cells.…”

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MMP19 is upregulated during melanoma progression and increases invasion of melanoma cells

Müller

Beck

Gadesmann³

et al. 2010

Modern Pathology

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During the progression of cutaneous melanomas, matrix metalloproteinases (MMPs) facilitate the tumour cells to traverse the basement membrane and invade the dermis. In this study, we analysed the expression of MMP19 in the course of melanoma progression. Although MMP19 was absent in melanocytes and melanoma cells of early stages of melanoma development, its expression was strongly upregulated in the neighbouring keratinocytes that may facilitate the vertical outgrowth of melanoma cells. In contrast to early stages, MMP19 was upregulated during the vertical growth phase of melanoma and in metastases. The upregulation of MMP19 in melanoma of Clark levels IV and V correlates with that of MMP2 and also simultaneously with ceased expression of E-cadherin. To reveal whether MMP19 facilitates the invasion of melanomas, we examined adhesion and migratory capacity of selected melanoma cell lines. Melanoma cell lines with low expression of MMP19 exhibited increased adhesion to various substrates and lower migration in comparison with the cell line with higher expression of MMP19. Moreover, ectopic expression of MMP19 could restore the migratory capacity of melanoma cells with low endogenous level of MMP19. These results suggest that the increase of MMP19 expression hallmarks the progression of cutaneous melanoma and might augment melanoma growth by promoting the invasion of tumour cells.

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Matrix metalloproteinases 19 and 20 cleave aggrecan and cartilage oligomeric matrix protein (COMP)

Cited by 121 publications

References 43 publications

ADAMTS‐7: a metalloproteinase that directly binds to and degrades cartilage oligomeric matrix protein

ADAMTS‐7: a metalloproteinase that directly binds to and degrades cartilage oligomeric matrix protein

Catalytic activity of matrix metalloproteinase‐19 is essential for tumor suppressor and anti‐angiogenic activities in nasopharyngeal carcinoma

MMP19 is upregulated during melanoma progression and increases invasion of melanoma cells

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