Secretion of gelatinases and tissue inhibitors of metalloproteinases by human lung cancer cell lines and revertant cell lines: Not an invariant correlation with metastasis

Zucker, Stanley; Lysik, Rita M.; Malik, M. H. A.; Bauer, B.; Caamaño, Jorge; Klein‐Szanto, Andres J.

doi:10.1002/ijc.2910520307

Cited by 42 publications

(21 citation statements)

References 13 publications

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“…From 75% [15] to 85% [8] of breast cancers have been shown to overexpress MMP-2, while Sato et al [27] demonstrated high MMP-9 expression in six of nine mesenchymal tumors studied. Some lung cancer cell lines have also been shown to overexpress MMP-2 and/or MMP-9 [28][29][30]. We demonstrated that all NSCLC cell lines studied overexpress MMP-2 and were characterized by proteolytic activity to type IV collagen.…”

Section: Discussionmentioning

confidence: 79%

Expression of Matrix Metalloproteinases and Tissue Inhibitor of Matrix Metalloproteinases in Non-Small-Cell Lung Cancer

Suzuki

Iwamoto

Fujisawa

et al. 1998

Invasion Metastasis

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Expression of matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of metalloproteinases (TIMP)-1, and TIMP-2 was studied in non-small-cell lung cancer (NSCLC). Activity of MMP-2 and MMP-9 by gelatin zymography and expression of MMP-2, MMP-9, TIMP-1, and TIMP-2 mRNAs were examined in 11 lung cancer cell lines which included six small-cell lung cancer (SCLC) cell lines. Localization of MMP-2, MMP-9, TIMP-1, and TIMP-2 was examined by immunohistochemistry in 43 resected NSCLC (22 adenocarcinomas, 17 squamous cell carcinomas, 4 large cell carcinomas) using specific anti-human monoclonal antibodies. Expression of MMP-2 mRNA was detected in 5 (100%), MMP-9 in 1 (20%), TIMP-1 in 4 (80%), and TIMP-2 in 5 (100%) of 5 NSCLC cell lines examined. MMP-2 gelatinolytic activity also was detected in all five NSCLC cell lines, whereas MMP-9 activity was detected in only one cell line. In 43 patients, MMP-2, MMP-9, TIMP-1, and TIMP-2 immunoreactivity was demonstrated in 19 (44%), 9 (21%), 15 (35%), and 29 (67%) excised tumors, respectively. All stromal fibroblasts in tumor samples stained positive for MMP-2. There was a correlation between TIMP-2 immunoreactivity and disease stage (42% stage I versus 88% stages II, III, and IV) (p = 0.0024). Both cancer cell lines and NSCLC tumor samples frequently expressed MMP-2, MMP-9, TIMP-1, and TIMP-2; MMP-2 in particular was highly expressed in malignant cells and surrounding fibroblasts. These findings suggest that MMP-2 plays a more important role in invasion of NSCLC than MMP-9 and that TIMP-2 may have clinical relevance in NSCLC.

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Section: Discussionmentioning

confidence: 79%

Expression of Matrix Metalloproteinases and Tissue Inhibitor of Matrix Metalloproteinases in Non-Small-Cell Lung Cancer

Suzuki

Iwamoto

Fujisawa

et al. 1998

Invasion Metastasis

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“…Other experimental studies employing cancer cells transfected with TIMP-1 cDNA demonstrated that MMPs may act primarily to alter the extracellular environment to allow sustained growth in an ectopic site as opposed to having a speci®c role in allowing the cells to extravasate from the blood stream (Cameron et al, 2000;Chambers and Matrisian, 1997;Nelson et al, 2000). In some experimental tumor systems, however, increased MMP production did not correlate with increased metastasis (Zucker et al, 1992). One potential explanation is that excess proteolysis may degrade matrix signals and receptors, thereby disrupting cell matrix interactions and inhibiting migration (Parks and Mecham, 1998).…”

Section: Atypical Aspects Of Mmp/timp Function In Cancermentioning

confidence: 99%

Critical appraisal of the use of matrix metalloproteinase inhibitors in cancer treatment

2000

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“…Quantitation of gelatinase A (both latent and activated enzyme detected), stromelysin-1, interstitial collagenase, TIMP-1, and TIMP-2 was performed on HUVEC-conditioned media using enzyme-linked immunosorbent assays as described previously (36,37).…”

Section: Zymography and Protein Studiesmentioning

confidence: 99%

Thrombin Induces the Activation of Progelatinase A in Vascular Endothelial Cells

Zucker

Conner

DiMassmo

et al. 1995

Journal of Biological Chemistry

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179

130

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Angiogenesis requires degradation of vascular basement membrane prior to migration and proliferation of endothelial cells; proteinases are essential ingredients in this process. Because of thrombin's multiple effects on endothelium, we have examined its role in matrix metalloproteinase activation using human umbilical vein endothelial cells. Gelatin zymography of endothelial conditioned media revealed a prominent 72-kDa progelatinase A band. Addition of ␣-thrombin to endothelial cells resulted in the generation of 64 and 62 kDa gelatinolytic bands which is consistent with the activation of progelatinase A; thrombin had no effect in the absence of cells. This effect requires the proteolytic site of thrombin since progelatinase A activation was abolished by specific inhibitors of thrombin. Matrix metalloproteinase inhibitors diminished thrombin-induced activation of progelatinase A. Pretreatment of endothelial cells with excess tissue inhibitor of metalloproteinase-2 or a COOH-terminal fragment of progelatinase A abrogated thrombin-mediated activation of progelatinase A presumably by competing with the COOH terminus of native progelatinase A for interaction with an activator site on endothelial plasma membranes. Although membrane-type matrix metalloproteinase was demonstrated in endothelial cells by Northern and Western blotting, the receptor function of this molecule in thrombin-induced activation of progelatinase A needs to be clarified. Progelatinase A activation did not require intracellular signal transduction events mediated by the thrombin receptor. These data demonstrate that 1) endothelial cells express a novel activation mechanism for progelatinase A, 2) proteolytically active thrombin regulates this activation mechanism, and 3) activation occurs independently of the functional thrombin receptor.Whereas the effect of thrombin (EC 3.4.21.5) on production of fibrin and activation of platelets has been intensively studied over many years, interest in the role of thrombin on endothelial function has lagged. Recent studies have indicated that thrombin affects post-clotting events involved in angiogenesis (1). The vascular endothelium actively binds coagulation proteins, resulting in cell-surface generation of thrombin that can persist within the protected environment of a clot (2). A unique Gprotein-coupled thrombin receptor (3) is known to be functionally expressed by endothelial cells (4). Interaction of thrombin with an endothelial cell-surface thrombin receptor(s) results in a multiplicity of effects including cell retraction and permeability, generation of phosphoinositides and prostaglandin, and secretion of Von Willebrand factor, tissue plasminogen activator, and platelet-derived growth factor (5-7). The role of individual thrombin receptors and endothelial signal transduction events on thrombin-mediated cell activation phenomena remain incompletely characterized (4).Neoangiogenesis, the formation of new blood vessels from preexisting vessels, requires the degradation of underlying basement membranes p...

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Secretion of gelatinases and tissue inhibitors of metalloproteinases by human lung cancer cell lines and revertant cell lines: Not an invariant correlation with metastasis

Cited by 42 publications

References 13 publications

Expression of Matrix Metalloproteinases and Tissue Inhibitor of Matrix Metalloproteinases in Non-Small-Cell Lung Cancer

Expression of Matrix Metalloproteinases and Tissue Inhibitor of Matrix Metalloproteinases in Non-Small-Cell Lung Cancer

Critical appraisal of the use of matrix metalloproteinase inhibitors in cancer treatment

Thrombin Induces the Activation of Progelatinase A in Vascular Endothelial Cells

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