Gelatinase-mediated migration and invasion of cancer cells

Björklund, Mikael; Koivunen, Erkki

doi:10.1016/j.bbcan.2005.03.001

Cited by 453 publications

(627 citation statements)

References 552 publications

(582 reference statements)

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“…Our data do not exclude the interpretation of previous studies, stating the great effect of host cell -derived gelatinases on aspects of tumor progression (8,9,12,28,34,43). In addition to this possibility, we could now attribute an important function to tumor cell -derived gelatinases, as well as assign distinct roles in invasion (mainly a function of MMP-9) and outgrowth of metastases (mainly a function of MMP-2).…”

Section: Discussionmentioning

confidence: 34%

“…Expression of MMP-2 and MMP-9 was detected in tumor and/or host cells of clinical and experimental specimen at end points of tumor development and synchronous colorectal cancer liver metastases, i.e., metastatic foci which were detectable at the time point of primary tumor surgery (16)(17)(18)(19). Although MMP-2 and MMP-9 are recognized as crucial contributors to liver metastasis (8,9), they were thus far not distinguishable regarding their respective function during different dynamic phases of tumor progression.…”

Section: Introductionmentioning

confidence: 99%

“…Based on structural features, MMP-2 and MMP-9 represent the subgroup called gelatinases, as they both harbor three gelatin-binding type II fibronectin domains in the catalytic domain (1,5). This is the basis of their common substrate specificity (5), including their ability to cleave collagen IV, the major component of gelatin or of basement membranes which underlie epithelial and endothelial cell layers (7)(8)(9). Consequently, the gelatinases were shown to be important determinants of tumor progression (8,(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

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Distinct Functionality of Tumor Cell–Derived Gelatinases during Formation of Liver Metastases

Gerg

Kopitz²,

Schaten³

et al. 2008

Molecular Cancer Research

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The specific spatiotemporal role of the matrix metalloproteinase 2 (MMP-2) and MMP-9 (gelatinase) during metastasis is still under debate. Host cells have been described as major contributors to these MMPs during metastasis. Here, we show strong overexpression of MMP-2 and MMP-9 by tumor cells of clinical liver specimen of recurrent metachronous metastases, leading us to address the importance of tumor cell -derived MMP-2 or MMP-9 during liver metastasis. Thus far, distinction of their roles was impossible due to lack of inhibitors which can act exclusively on tumor cells or distinguish MMP-2 from MMP-9. We therefore used short hairpin RNA interference technology in the well-established syngeneic L-CI.5s lymphoma model, in which we could analyze the time course of experimental liver colonization (arrest/invasion of single tumor cells, outgrowth, and invasion within the parenchyma) in immunocompetent mice and correlate these steps with MMP-2 or MMP-9 expression levels. In parental tumor cells, MMP-9 expression closely correlated with the invasive phases of liver colonization, whereas MMP-2 expression remained unaltered. Specific knockdown of MMP-9 revealed a close correlation between invasion-dependent events and tumor cell -derived MMP-9 expression. In contrast, knockdown of MMP-2 did not significantly alter the metastatic potential of the cells but led to a marked inhibition of metastatic foci growth. These findings explain the efficacy of gelatinase-specific synthetic inhibitors on invasion and growth of tumor cells and attribute distinct functions of MMP-2 and MMP-9 to aspects of liver metastasis. (Mol Cancer Res 2008;6(3):341 -51)

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Section: Discussionmentioning

confidence: 34%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Distinct Functionality of Tumor Cell–Derived Gelatinases during Formation of Liver Metastases

Gerg

Kopitz²,

Schaten³

et al. 2008

Molecular Cancer Research

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“…They considerably differ in their expression profiles: MMP-2 is constitutively released in physiological conditions, whereas MMP-9 is highly inducible. Both enzymes are often expressed in the tumor microenvironment where they contribute to both malignant transformation and tumor invasiveness by modulating bioavailability of growth factors and by shedding adhesion molecules and basement membrane components (15,16).…”

Section: Introductionmentioning

confidence: 99%

Enzymatic processing by MMP‐2 and MMP‐9 of wild‐type and mutated mouse β‐dystroglycan

et al. 2012

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SummaryDystroglycan (DG) is a membrane-associated protein complex formed by two noncovalently linked subunits, a-DG, a highly glycosylated extracellular protein, and b-DG, a transmembrane protein. The interface between the two DG subunits, which is crucial to maintain the integrity of the plasma membrane, involves the C-terminal domain of a-DG and the N-terminal extracellular domain of b-DG. It is well known that under both, physiological and pathological conditions, gelatinases (i.e. MMP-9 and/or MMP-2) can degrade DG, disrupting the connection between the extracellular matrix and the cytoskeleton. However, the molecular mechanisms and the exact cleavage sites underlying these events are still largely unknown. In a previous study, we have characterized the enzymatic digestion of the murine b-DG ectodomain by gelatinases, identifying a main cleavage site on the b-DG ectodomain produced by MMP-9. In this article, we have deepened the pattern of the b-DG ectodomain digestion by MMP-2 by using a combined approach based on SDS-PAGE, Orbitrap, and HPLC-ESI-IT mass spectrometry. Furthermore, we have characterized the kinetic parameters of the digestion of some b-DG ectodomain mutants by gelatinases.2012 IUBMB IUBMB Life, 64(12): 988-994, 2012

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“…7 MMP family, MMP2 and -9 have major roles in degradation of ECM during tumor invasion. 8 MMPs such as gelatinase and stromelysin, which are secreted into ECM, are inactivated by α2-macroglobulin or tissue inhibitor of metalloprotease (TIMP). 9 There is a tight balance between MMPs and TIMP in ECM formation.…”

Section: Introductionmentioning

confidence: 99%

Changes of the Expressions of Orphan and gon- ADAMTS in Chondrosarcoma Cells

Işık¹

2015

UHOD

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Some of A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) enzymes have been suggested to facilitate invasion and metastasis in cancer. ADAMTS20 is called gon-ADAMTS and ADAMTS10 and -17 are called orphan ADAMTSs. ADAMTS20 degrades versican and aggrecan in extracellular matrix. We aimed to investigate the effects of insulin on ADAMTS10,-17 and -20 in OUMS-27 chondrosarcoma cells. OUMS-27 cells were cultured in Dulbecco's modified Eagle' medium (DMEM) containing 10 μg/mL insulin. The medium was changed every other day up to 11th day. Cells were harvested at 1, 3, 7, and 11th days and RNA isolation was performed at appropriate times according to study setup. The levels of RNA expression of ADAMTS10,-17 and -20 were estimated by qRT-PCR using appropriate primers. ADAMTS10 mRNA expression gradually decreased within 7 days after insulin induction compared to control group. There was a significant difference between control and Day 7 groups (p=0.021) as well as Day 1 and Day 7 groups (p=0.028). ADAMTS17 mRNA expression increased right after insulin induction at day 1 compared to control group and protected its high levels throughout insulin application. The most evident and statistically significant increase in mRNA concentration was observed at day 7 after insulin induction (p= 0.014). Our results demonstrated that ADAMTS10,-17 and -20 might have a role in cancer progression. Although functions of ADAMTS10 and -17 are not known, their expression levels have changed in chondrosarcoma cell line. Further studies are needed to characterize chondrosarcoma cells because of the possible association between cancer progression and ADAMTS proteins. Keywords: ADAMTS, Chondrosarcoma, Insulin, qRT-PCR, OUMS-27 ÖZET Kondrosarkom Hücrelerinde Orfan ve gon-ADAMTS'ların Ekspresyonundaki DeğişimlerA disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) enzimlerinden bazılarının kanserde invazyon ve metastazı kolaylaştıracağı öngörülmektedir. ADAMTS20, gon-ADAMTS olarak ve ADAMTS10 ile -17, orfan ADAMTS olarak adlandırılır. Bunlardan ADAMTS20 hücre dışı matrikste versikan ve agrekanı parçalayan enzim olarak bilinir. Bu çalışmada OUMS-27 hücrelerinde insülinin ADAMTS10, -17 ve -20 üzerine etkilerinin araştırılması amaçlandı. OUMS-27 hücreleri 10 μg/ml insülin içeren Dulbecco's Modified Eagle Medium (DMEM) ortamında kültüre edildiler. Medyum 11. güne kadar iki günde bir değiştirildi. Hücreler 1, 3, 7 ve 11. günlerde toplandı ve her birinde aynı gün RNA izolasyonları gerçekleştirildi. ADAMTS10, -17 ve -20'nin RNA ekspresyon düzeyleri uygun primerler kullanılarak qRT-PCR ile hesaplandı. Kontrol grubuyla karşılaştırıldığında, ADAMTS10 mRNA ekspresyonu insülin indüksiyonundan sonra 7 gün içinde gittikçe azalmıştır. Kontrol ile 7. gün grubu arasında (p=0.021) ve 1. gün ve 7. gün grubu (p=0.028) arasında anlamlı farklılıklar vardı. Kontrol grubuyla karşılaştırıldığında ADAMTS17 mRNA ekspresyonu insülin indüksiyonundan hemen sonra 1. günde yükselmiş ve yüksek seviyelerini insülin uygulaması boyunca k...

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Gelatinase-mediated migration and invasion of cancer cells

Cited by 453 publications

References 552 publications

Distinct Functionality of Tumor Cell–Derived Gelatinases during Formation of Liver Metastases

Distinct Functionality of Tumor Cell–Derived Gelatinases during Formation of Liver Metastases

Enzymatic processing by MMP‐2 and MMP‐9 of wild‐type and mutated mouse β‐dystroglycan

Changes of the Expressions of Orphan and gon- ADAMTS in Chondrosarcoma Cells

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