A matrix metalloproteinase expressed on the surface of invasive tumour cells

Sato, Hiroshi; Takino, Takahisa; Okada, Yasunori; Cao, Jian; Shinagawa, Akira; Yamamoto, Etsuhide; Seiki, Motoharu

doi:10.1038/370061a0

Cited by 2,388 publications

(1,916 citation statements)

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“…Thus expression and secretion of protein product may not, in all cases, be the chief arbiters of functionality (Azzam et al, 1993). For instance, activation of pro-72 kDa gelatinase A (MMP-2) involves binding of the pro-MMP2/ TIMP-2 complex to a cell-surface receptor followed by proteolytic cleavage by a transmembrane metalloproteinase (MT-MMP-1), thereby restricting MMP-2 activity to the pericellular environment of cells carrying appropriate activation machinery (Emonard et al, 1992;Monsky et al, 1993;Kleiner and Stetler-Stevenson, 1993;Sato et al, 1994;Vassalli and Pepper, 1994 et al, 1993). Thus, the processes that control cell proliferation and invasion are to some degree, independent.…”

Section: Discussionmentioning

confidence: 99%

Comparative analysis of the expression patterns of metalloproteinases and their inhibitors in breast neoplasia, sporadic colorectal neoplasia, pulmonary carcinomas and malignant non-Hodgkin's lymphomas in humans

Kossakowska

Huchcroft²,

Urbanski³

et al. 1996

Br J Cancer

119

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Summary Matrix metalloproteinases (MMPs) and their inhibitors (tissue inhibitors of metalloproteinases, TIMPs) play essential roles in the remodelling of the extracellular matrix (ECM). Results of in vivo and in vitro studies suggest that the balance between MMPs and TIMPs is altered in neoplasia, contributing to the invasive and metastatic properties of malignant tumours. In this study we have analysed the expression of five MMP genes and TIMP-1 and TIMP-2 in 37 benign and malignant lesions of human breast using Northern blot analysis. MMP-9 (92 kDa gelatinase) and MMP-l (stromelysin 3) were most consistently expressed by carcinomas. Based on detection of either MMP-9 or MMP-l mRNAs, we were able to distinguish between malignant and benign disease with a predictive accuracy of 90% with 94% sensitivity and 85% specificity. Subsequently, these results were compared with results for carcinomas of colon and lung and malignant nonHodgkin's lymphomas (NHL). Elevated MMP-9 and TIMP-1 expression was observed in all four systems. MMP-l characterised all carcinomas as well as carcinomas in situ but was not detectable in NHL. Our data therefore argue that there are remarkably similar patterns of specific functions involved in ECM remodelling that correlate with malignancy in different human tumours of different histogenesis. However, MMP-l expression is a characteristic of tumours of epithelial origin that is not found in lymphoid neoplasia. Thus it suggests that MMP-l may play a regulatory role in the invasion and metastasis of carcinomas.

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Section: Discussionmentioning

confidence: 99%

Comparative analysis of the expression patterns of metalloproteinases and their inhibitors in breast neoplasia, sporadic colorectal neoplasia, pulmonary carcinomas and malignant non-Hodgkin's lymphomas in humans

Kossakowska

Huchcroft²,

Urbanski³

et al. 1996

Br J Cancer

119

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“…Membrane-bound MMP14 activates secreted MMP2 by cleaving its prodomain 51,52 . Indeed, active MMP2 is significantly decreased in Mmp14-null mice, strongly indicating that MMP2 is an in vivo substrate of MMP14 (REF.…”

Section: Human Mmp Mutations Lead To Defects In Bone Developmentmentioning

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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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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“…Although the specific binding of gelatinase A to the surface of tumor and normal fibroblast cells has been described, a membrane protein that functions as a gelatinase A receptor in the relevance to the activator has not been identified. We molecularly cloned a new matrix metalloproteinase (MMP) gene, of which the product was associated with the proteolytic activation of progelatinase A [14,15]. Since this MMP has a transmembrane domain and localizes on the cell surface, it was named membrane-type MMP (recently renamed membrane-type-l-MMP, MT1-MMP).…”

Section: Introductionmentioning

confidence: 99%

“…MT1-MMP is overexpressed in malignant tumor tissues, including lung and stomach carcinomas that contain activated gelatinase A. This suggests that MT1-MMP is associated with the activation of progelatinase A in these tumor tissues [14,16,17]. MT1-MMP expression has been detected in HT-1080 cells treated with TPA and MDA-MB-231 cells stimulated with concanavalin A, which induce progelatinase A activation [18,19].…”

Section: Introductionmentioning

confidence: 99%