Matrix Metalloproteinases

Nagase, Hideaki; Woessner, Jeff

doi:10.1074/jbc.274.31.21491

Cited by 3,793 publications

(3,023 citation statements)

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“…Expression of several MMP genes is inducible with growth factors and cytokines including EGF (Nagase and Woessner, 1999;Westermarck and Ka¨ha¨ri, 1999). We showed that expressions of MMP-1, -3, -9 and -10 are inducible in T24 cells with EGF.…”

Section: Discussionmentioning

confidence: 78%

Requirement of STAT3 activation for maximal collagenase-1 (MMP-1) induction by epidermal growth factor and malignant characteristics in T24 bladder cancer cells

et al. 2005

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Signal transducers and activators of transcription (STATs) are latent transcription factors that mediate cytokine-and growth factor-induced transcription. Constitutive activation of STAT3 has been shown in human cancers and transformed cell lines. We report that STAT3, but not STAT1 and STAT5, becomes phosphorylated in response to epidermal growth factor (EGF) and achieves maximal induction of collagenase-1 (MMP-1) transcription by interacting with c-JUN. Phosphorylation of STAT3 protein is biphasic: the first peak within 30 min and the second peak between 4 and 8 h. Association of STAT3 with c-JUN is detected and its constituting STAT3 is increasingly phosphorylated. The STAT and AP-1 elements are necessary for effective induction of MMP-1 promoter by EGF. Mutation of AP-1 element closely located at the STAT site abolishes the binding not only of c-JUN but also of STAT3 to MMP-1 promoter, resulting in the loss of the responsiveness to EGF. By blocking STAT3 activity with the dominant-negative form, we show the requirement of STAT3 for EGF induction of MMP-1 and MMP-10 (stromelysin-2). Furthermore, expression of the dominant-negative STAT3 is sufficient to inhibit the constitutive and EGF-inducible cell migration and invasion and the tumor formation in nude mice. These results demonstrate that STAT3 phosphorylation and its possible interaction with c-JUN are required for the strong responsiveness of MMP-1 to EGF, and STAT3 activation is crucial for exhibition of malignant characteristics in T24 bladder cancer cells.

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Section: Discussionmentioning

confidence: 78%

Requirement of STAT3 activation for maximal collagenase-1 (MMP-1) induction by epidermal growth factor and malignant characteristics in T24 bladder cancer cells

et al. 2005

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“…MMP-9 has been associated with invasion and metastasis because of its potency to degrade gelatin and type IV collagen 8 as major components of basement membranes. To assess the clinical impact of MMP-9 expression on long-term survival in patients with operable NSCLC, an immunohistochemical study of MMP-9 expression by primary tumors was carried out.…”

Section: Discussionmentioning

confidence: 99%

“…8,13 To date, activity of MMPs in tissue sections can only be measured using in situ zymography. 17,18 For this method however, fresh cryosections of primary tumors are needed.…”

Section: Discussionmentioning

confidence: 99%

“…7 One group of proteolytic enzymes that has been associated with these abilities is the matrix metalloproteinase family (MMP). Matrix metalloproteinase 9 (MMP-9) (92 kDa Type IV collagenase or gelatinase B) has the potency to degrade gelatin and Type IV collagen, 8 which is a major component of basement membranes. The clinical relevance of MMP 9 in NSCLC remains in discussion.…”

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confidence: 99%

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Prognostic impact of matrix metalloproteinase‐9 in operable non‐small cell lung cancer

Sienel¹,

Hellers²,

Morresi‐Hauf³

et al. 2002

Intl Journal of Cancer

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We assessed the clinical impact of MMP-9 expression on long-term survival in patients with operable non-small cell lung cancer (NSCLC). Primary tumors of 143 consecutive patients with NSCLC resected completely and without overt distant metastases (pT1-4, pN0-2, M0, R0) were examined for MMP-9 expression using immunohistochemistry with a polyclonal, affinity-purified rabbit antibody that recognizes both latent and active MMP-9. Immunohistochemical staining of tumor cells was evaluated in comparison to normal bronchiolar epithelium that served as an internal positive control. MMP-9 expression was categorized into negative, <5% tumor cells stained; heterogeneous, >5% and <95% tumor cells stained; and homogeneous, >95% The standard treatment for early stage NSCLC is surgery resulting in a 5-year survival rate of only 50 -60% in Stage I and II. 5,6 A better understanding of the molecular mechanisms of lung cancer progression might help to identify patients at risk for an unfavorable outcome with potential consequences for adjuvant therapy.Penetration of basement membranes and degradation of extracellular matrix are essential steps in the dissemination of tumor cells from primary tumors to distant organs. 7 One group of proteolytic enzymes that has been associated with these abilities is the matrix metalloproteinase family (MMP). Matrix metalloproteinase 9 (MMP-9) (92 kDa Type IV collagenase or gelatinase B) has the potency to degrade gelatin and Type IV collagen, 8 which is a major component of basement membranes. The clinical relevance of MMP 9 in NSCLC remains in discussion. First clinical trials investigating the efficacy of MMP-inhibitors in advanced cancer were rather disappointing. 9 Furthermore, previous studies examining the prognostic impact of immunohistochemical detection of MMP-9 in NSCLC 10,11 are discussed controversially because they did not demonstrate an independent prognostic impact of MMP-9 considering all standard prognostic factors included in the international system for staging lung cancer. 6 To clarify the prognostic impact of MMP 9 in operable NSCLC, we applied a new immunohistochemical evaluation system, focusing on homogeneous expression of MMP-9. The prognostic value was analyzed in relation to established prognostic factors of the TNM-system. Our study shows that the prognostic impact of homogeneous MMP-9 expression remains independent from possible prognostic joint effects of pT-status, pN-status, tumor histology and tumor grading. Because of this independence, MMP-9 may be considered as an interesting target for adjuvant anticancer therapy in operable NSCLC using selective MMP-inhibitors with high specificity for MMP-9. MATERIAL AND METHODS PatientsAfter approval by the ethical committee of the University of Munich and after written informed consent, tissue specimens of 147 consecutive patients with completely resected NSCLC were collected. The tumors were classified according to the international union against cancer (UICC) TNM-classification. 6 The preoperative staging of all patient...

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“…19,20 In this regard, they are dissimilar from a group of bacterial proteinases that evolved a strict specificity for human IgA. 21 Also, IgG fragmentation with human and most bacterial proteinases has generally been found to be slower than with papain or pepsin.…”

Section: Introductionmentioning

confidence: 99%

Proteinase-nicked IgGs: an unanticipated target for tumor immunotherapy

et al. 2018

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The host immune system adopts multiple mechanisms involving antibodies to confront cancer cells. Accordingly, anti-tumor mAbs have become mainstays in cancer treatment. However, neither host immunity nor mAb therapies appear capable of controlling tumor growth in all cases. Structural instability of IgG was overlooked as a factor contributing to immunosuppression in the tumor microenvironment. Recently, physiological proteinases were identified that disable IgG immune effector functions. Evidence shows that these proteinases cause localized IgG impairment by selective cleavage of a single IgG peptide bond in the hinge-region. The recognition of IgG cleavage in the tumor microenvironment provides alternatives for tumor immunotherapy.

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Matrix Metalloproteinases

Cited by 3,793 publications

References 85 publications

Requirement of STAT3 activation for maximal collagenase-1 (MMP-1) induction by epidermal growth factor and malignant characteristics in T24 bladder cancer cells

Requirement of STAT3 activation for maximal collagenase-1 (MMP-1) induction by epidermal growth factor and malignant characteristics in T24 bladder cancer cells

Prognostic impact of matrix metalloproteinase‐9 in operable non‐small cell lung cancer

Proteinase-nicked IgGs: an unanticipated target for tumor immunotherapy

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