Matrix metalloproteinases 2 and 9 (gelatinases A and B) expression in malignant mesothelioma and benign pleura

Edwards, John; McLaren, J.; Jones, J. Louise; Waller, David; O’Byrne, Kenneth J.

doi:10.1038/sj.bjc.6600920

Cited by 60 publications

(61 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…1-3). MMP-2/gelatinase A is the most abundant MMP and a marker of poor prognosis in various cancer types (4)(5)(6). MMPs are synthesized as preproenzymes and activated by proteolytic processing.…”

Section: Introductionmentioning

confidence: 99%

Activated Leukocyte Cell Adhesion Molecule (ALCAM/CD166/MEMD), a Novel Actor in Invasive Growth, Controls Matrix Metalloproteinase Activity

et al. 2005

View full text Add to dashboard Cite

Activated leukocyte cell adhesion molecule (ALCAM/CD166/ MEMD) could function as a cell surface sensor for cell density, controlling the transition between local cell proliferation and tissue invasion in melanoma progression. We have tested the hypothesis that progressive cell clustering controls the proteolytic cascade for activation of gelatinase A/matrix metalloproteinase-2 (MMP-2), which involves formation of an intermediate ternary complex of membrane type 1 MMP (MT1-MMP/MMP-14), tissue inhibitor of metalloproteinase-2 (TIMP-2), and pro-MMP-2 at the cell surface. Surprisingly, truncation of ALCAM severely impaired MMP-2 activation in a nude mouse xenograft model, in which we previously observed diminished primary tumor growth and enhanced melanoma metastasis. Comparative studies of twodimensional monolayer and three-dimensional collagen-gel cultures revealed that extensive cell-to-cell contacts, wildtype ALCAM, and cell-to-matrix interactions were all indispensable for efficient conversion of pro-MMP-2 to its active form in metastatic melanoma cells. Truncated, dominantnegative ALCAM diminished MMP-2 activation via reduced transcript levels and decreased processing of MT1-MMP. Failure of the proteolytic cascade after selective ALCAM depletion by RNA interference was mainly due to incomplete MT1-MMP processing, which was otherwise promoted by extensive cell-to-cell contacts. These data attribute a novel signaling role to ALCAM in regulation of proteolysis and support its previously postulated sensor function in invasive growth. (Cancer Res 2005; 65(19): 8801-8)

show abstract

Section: Introductionmentioning

confidence: 99%

Activated Leukocyte Cell Adhesion Molecule (ALCAM/CD166/MEMD), a Novel Actor in Invasive Growth, Controls Matrix Metalloproteinase Activity

et al. 2005

View full text Add to dashboard Cite

show abstract

“…MMP2 is the only MMP identified in MM exosomes (4). MMP2 levels, measured in tissue homogenates, are a negative prognostic indicator in MM (59). Thus, this study suggests that MM is characterized by an increase in the activity of MMPs, particularly exosome secreted MMP2, which may be due to decreased TIMP1 expression and activation by QSOX1 as discussed previously.…”

Section: Cancer Genomics and Proteomicsmentioning

confidence: 74%

A Proteomic Analysis of the Malignant Mesothelioma Secretome Using iTRAQ

Creaney

Dick

Leon

et al. 2017

CGP

View full text Add to dashboard Cite

show abstract

“…Substantial evidence links MMP expression to tumor invasion in many different tumors (5)(6)(7)(8)(9)(10). In addition, clinical studies note the association of matrix metalloproteinase (MMP) expression with progression of malignant mesothelioma (11,12) and lung cancer (13,14).…”

Section: Introductionmentioning

confidence: 99%

Modulation of MMP-2 and MMP-9 by cytokines, mitogens and inhibitors in lung cancer and malignant mesothelioma cell lines

Roomi

Monterrey²,

Kalinovsky³

et al. 2009

Oncol Rep

View full text Add to dashboard Cite

Abstract. Matrix metalloproteinases (MMPs) secreted by lung cancer (LC) and malignant mesothelioma (MM), especially MMP-2 and MMP-9, play crucial roles in tumor invasion and metastasis. We examined the effect of cytokines, mitogens and inhibitors on MMP-2 and MMP-9 expression in LC and MM cell lines. Human LC (A-549) and MM (MSTO-211H) cell lines were cultured in appropriate media. At near confluence, the cells were washed with PBS and incubated in serum-free medium with various concentrations of several cytokines, mitogens and inhibitors. After 24 h the media were removed and analyzed for MMP-2 and MMP-9 by gelatinase zymography and quantitated by densitometry. LC expressed MMP-2 whereas MM expressed MMP-2 and MMP-9. TNF-·, IL-1ß, LPS and PMA, stimulated MMP-2 in LC and inhibited MMP-2 in MM, but had no effect on MMP-9. Doxycycline, EGCG and NM inhibited MMP-2 and MMP-9 expression, in both cell lines. Actinomycin-D, cyclohexamide, retinoic acid and dexamethasone inhibited MMP-2 in both cancer cell lines and inhibited MMP-9 in MM. Our results show that cytokines and inhibitors have an up-or downregulatory effect on MMP-2 and MMP-9 expression in LC and MM, suggesting the clinical value of targeting these proteases for management of LC and MM and their pathogenesis.

show abstract

Matrix metalloproteinases 2 and 9 (gelatinases A and B) expression in malignant mesothelioma and benign pleura

Cited by 60 publications

References 55 publications

Activated Leukocyte Cell Adhesion Molecule (ALCAM/CD166/MEMD), a Novel Actor in Invasive Growth, Controls Matrix Metalloproteinase Activity

Activated Leukocyte Cell Adhesion Molecule (ALCAM/CD166/MEMD), a Novel Actor in Invasive Growth, Controls Matrix Metalloproteinase Activity

A Proteomic Analysis of the Malignant Mesothelioma Secretome Using iTRAQ

Modulation of MMP-2 and MMP-9 by cytokines, mitogens and inhibitors in lung cancer and malignant mesothelioma cell lines

Contact Info

Product

Resources

About