Regulation of matrix metalloproteinase-9 and inhibition of tumor invasion by the membrane-anchored glycoprotein RECK

Matrix metalloproteinases (MMPs) were discovered because of their role in amphibian metamorphosis, yet they have attracted more attention because of their roles in disease. Despite intensive scrutiny in vitro, in cell culture and in animal models, the normal physiological roles of these extracellular proteases have been elusive. Recent studies in mice and flies point to essential roles of MMPs as mediators of change and physical adaptation in tissues, whether developmentally regulated, environmentally induced or disease associated.The founding member of the matrix metalloproteinase (MMP) family, collagenase, was identified in 1962 by Gross and Lapiere, who found that tadpole tails during metamorphosis contained an enzyme that could degrade fibrillar collagen 1,2 . Subsequently, an interstitial collagenase, collagenase-1 or MMP1, was found in diseased skin and synovium 3 . In vitro, MMP1 initiates degradation of native fibrillar collagens, crucial components of vertebrate extracellular matrix (ECM), by cleaving the peptide bond between Gly775-Ile776 or Gly775-Lys776 in native type I, II or III collagen molecules 3,4 . Further research led to the discovery of a family of structurally related proteinases (23 in human, 24 in mice), now referred to as the MMP family.Interest in MMPs increased in the late 1960s and early 1970s following observations that MMPs are upregulated in diverse human diseases including rheumatoid arthritis and cancer. Importantly, high levels of MMPs often correlated with poor prognosis in human patients (reviewed in REF. 5 ). However, recent clinical data indicate that the relationship between § These authors contributed equally to this paper. Competing interests statementThe authors declare no competing financial interests. DATABASESThe following terms in this article are linked online to: Entrez Genome: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene DmMmp1 | DmMmp2 NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptMMPs and disease is not simple; for example, increased MMP activity can enhance tumour progression or can inhibit it (reviewed in REF. 6 ). This complex relationship between MMP expression and cancer has increased the basic and clinical interest in understanding MMP function in vivo, but it has also focused attention on MMPs and pathology, and relatively less attention has been focused on the normal roles of these enzymes. MMP proteolysisMMPs are members of the metzincin group of proteases, which are named after the zinc ion and the conserved Met residue at the active site 11,12 . Recent work has generated a unified peptidase nomenclature 13 Functions of MMP proteolysisHistorically, MMPs were thought to function mainly as enzymes that degrade structural components of the ECM. However, MMP proteolysis can create space for cells to migrate, can produce specific substrate-cleavage fragments with independent biological activity, can MMPs in bone modelling and remodellingBone is an important site of ongoing tissue remodelling during development...

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“…• Epithelial-mesenchymal transition (EMT) [134][135][136][137][138] • Invasion and metastasis 29,138,139 • Vasoconstriction 140…”

Section: Box 2 Biological Consequences Of Mmp Proteolysismentioning

confidence: 99%

Matrix metalloproteinases and the regulation of tissue remodelling

Page-McCaw

Ewald

Werb

2007

Nat Rev Mol Cell Biol

2,585

2,180

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“…Reversion-inducing cysteine-rich protein with Kazal motifs (RECK) acts as a membrane-anchored metalloproteinase regulator [1][2][3][4] which functions as a regulator of extracellular matrix integrity in normal condition, contributing to tumor and metastasis suppressing agent. However, recent study found abundant expression of RECK in the cells associated with blood vessels undergoing rapid remodeling in the mouse implantation chambers, suggesting that RECK has a role in vascular remodeling which may involve non-sprouting mechanisms such as intussusception and pruning.…”

Section: Introductionmentioning

confidence: 99%

Expression of RECK in endothelial cells of glioma: comparison with CD34 and VEGF expressions

Rahmah

Sakai

et al. 2011

J Neurooncol

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2 AbstractPurpose: Angiogenesis is thought to involve in progression of glioma grades, and RECK has been said to involve in maturation of vessels. In this study, we aimed to determine whether high micro-vessel density (MVD) expressed by RECK in glioma tissue is correlated with grades of glioma. We also compared RECK expression with that of the formerly known vessel marker, CD34 and VEGF.Methods: RECK, CD34 and VEGF immuno-reactivities of 72 glioma tissues were studied.Results: RECK was seen in microvessels of glioma tissues. CD34 showed similar pattern to RECK, whereas VEGF showed positive staining in cytoplasm of tumor cells and endothelial cells. Average MVD with RECK was 107.6 microvessels (range: 7-290).RECK was positively correlated with grades of glioma. RECK and CD34 also showed strong correlation (P= 0.001). Higher frequency of VEGF staining was also correlated with higher grade of glioma.Conclusions: This is the first study describing expression of RECK in glioma, and its angiogenesis-related nature may provide a potential therapeutic target for glioma treatment in the future.

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“…In addition, subsequent evidence suggested that subdomain IV of the extracellular domain is important for dimerization and small peptides with cysteine knot topology is able to block dimer formation of HER-2/Neu [18]. RECK protein contains five putative cysteine knot motifs at the NH 2 -terminal region [1]. Therefore, RECK may use this region to interfere HER-2/ Neu dimer formation.…”

Section: Resultsmentioning

confidence: 99%

“…RECK was originally identified as a MMP inhibitor with little anti-proliferative activity on various tumor-derived cell lines, including HT1080 (sarcoma), B16 (melanoma), SW48 (colon cancer), A549 (lung cancer), HeLa (cervical cancer), and A673 (Ewing tumor) [1]. However, a recent study demonstrated that knockdown of RECK in human umbilical vein endothelial cells induced growth arrest and cellular senescence [20].…”

Section: Resultsmentioning

confidence: 99%

“…The RECK gene was isolated as a transformation suppressor gene by using an expression cloning strategy designed to identify human cDNA inducing flat reversion in a v-Ki-ras-transformed NIH/3T3 cell line [1]. This gene encodes a membrane glycoprotein that may inhibit tumor metastasis and angiogenesis by negatively regulating matrix metalloproteinase (MMP) activity [2].…”

Section: Introductionmentioning

confidence: 99%

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The tumor suppressor RECK interferes with HER-2/Neu dimerization and attenuates its oncogenic signaling

et al. 2011

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a b s t r a c tOur previous study demonstrates that HER-2/Neu oncogene inhibits a matrix metalloproteinase inhibitor and tumor metastasis suppressor RECK to promote metastasis. Conversely, the effect of RECK on the oncogenic function of HER-2/Neu is unknown. Ectopic expression of RECK in 293T cells and HER-2/Neu-overexpressing breast cancer cells shows that RECK and HER-2/Neu are co-localized and these two proteins can be co-immunoprecipitated. RECK inhibits HER-2/Neu receptor dimerization and autophosphorylation, which causes reduction of ERK and AKT kinase activity and downregulation of HER-2/Neu target genes. RECK expression is reduced in 58.8% of breast cancer tissues and is associated with lymph node invasion supporting its anti-metastatic role. Collectively, we provide the first evidence that RECK can negatively regulate oncogenic activity of HER-2/Neu by inhibiting receptor dimerization. Structured summary:HER-2/Neu physically interacts with HER-2/Neu by blue native page (View interaction) HER-2/Neu physically interacts with RECK by coimmunoprecipitation (View interaction) HER-2/Neu and RECK colocalize by fluorescence microscopy (View Interaction 1, 2) HER-2/Neu physically interacts with RECK by anti bait coimmunoprecipitation (View interaction)

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Regulation of matrix metalloproteinase-9 and inhibition of tumor invasion by the membrane-anchored glycoprotein RECK

Cited by 440 publications

References 33 publications

Matrix metalloproteinases and the regulation of tissue remodelling

Matrix metalloproteinases and the regulation of tissue remodelling

Expression of RECK in endothelial cells of glioma: comparison with CD34 and VEGF expressions

The tumor suppressor RECK interferes with HER-2/Neu dimerization and attenuates its oncogenic signaling

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