Overexpression of matrix metalloproteinase-2 mediates phenotypic transformation of lens epithelial cells

Seomun, Young; Kim, Jeong‐A; Lee, Eunjoo H.; Joo, Choun‐Ki

doi:10.1042/0264-6021:3580041

Cited by 42 publications

(38 citation statements)

References 41 publications

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“…40 Our study establishes that OTR4120 regulates the coexpression of collagen I and collagen III at cutaneous burn sites and suggests that this effect may involve a TGF-b1-related pathway. In addition, TGF-b1 induces MMP-2 production either directly 41 or by stimulating CTGF-induced MMP-2 activation. 42 Moreover, TGF-b1 contributes to stimulate MMP-9 expression.…”

Section: Discussionmentioning

confidence: 99%

RGTA OTR4120, a heparan sulfate mimetic, is a possible long‐term active agent to heal burned skin

Garcia-Filipe

Barbier-Chassefière

Alexakis

et al. 2006

J Biomedical Materials Res

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Burn-related skin fibrosis leads to loss of tissue function and hypertrophic scar formation with damaging consequences for the patient. There is therefore a great need for an efficient agent to treat burned skin. We report that ReGeneraTing Agent (RGTA) reduces burn-induced skin alteration. The tissue-regenerating effect of RGTA OTR4120 was evaluated after 1-6 days and after 10 months in a rat skin burn model. This effect was also examined in vitro using fibroblasts isolated from control and 6-day-old burned skins. We measured production of dermal collagen I, III, and V and activities of metalloproteinases 2 and 9 (MMP-2 and MMP-9). Ratio of collagen III over collagen I production increased 6 days after the burn, because of a decrease in collagen I production. After 10 months, ratio of collagen III over collagen I in burn sites was still increased compared with control skin, because of an increase in collagen III production. Both abnormalities were corrected by OTR4120. OTR4120 increased pro-and active MMP-2 and MMP-9, compared with healthy and burned controls and therefore accelerated remodeling. Similar data were obtained with cultured fibroblasts from healthy and burned skins. OTR4120 enhanced healing in short-and long-term after burns, reducing the formation of fibrotic tissue, and then represents a potential agent to improve burned skin healing.

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Section: Discussionmentioning

confidence: 99%

RGTA OTR4120, a heparan sulfate mimetic, is a possible long‐term active agent to heal burned skin

Garcia-Filipe

Barbier-Chassefière

Alexakis

et al. 2006

J Biomedical Materials Res

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“…Transforming growth factor-b1 has been shown to reduce the immune response (Beck et al, 2001), stimulate angiogenesis Derynck et al, 2001;Bertolino et al, 2005), increase synthesis of proteolytic enzymes (Seomun et al, 2001;Kim et al, 2004) and stimulate extra cellular matrix (ECM) deposition (Cheng and Lovett, 2003) in the tumour microenvironment.…”

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confidence: 99%

Tissue level, activation and cellular localisation of TGF-β1 and association with survival in gastric cancer patients

et al. 2007

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Transforming growth factor-b1 (TGF-b1), a tumour suppressing as well as tumour-promoting cytokine, is stored as an extracellular matrix-bound latent complex. We examined TGF-b1 activation and localisation of TGF-b1 activity in gastric cancer. Gastric tumours showed increased stromal and epithelial total TGF-b1 staining by immunohistochemistry. Active TGF-b1 was present in malignant epithelial cells, but most strongly in smooth muscle actin expressing fibroblasts. Normal gastric mucosa from the same patient showed some staining for total, and little for active TGF-b1. Active TGF-b1 levels were determined by ELISA on tissue homogenates, confirming a strong increase in active TGF-b1 in tumours compared to corresponding normal mucosa. Moreover, high tumour TGFb1 activity levels were significantly associated with clinical parameters, including worse survival of the patients. Total and active TGFb1 levels were not correlated, suggesting a specific activation process. Of the different proteases tested, active TGF-b1 levels were only correlated with urokinase activity levels. The correlation with urokinase activity suggests a role for plasmin in TGF-b1 activation in the tumour microenvironment, resulting in transformation of resident fibroblasts to tumour promoting myofibroblasts. In conclusion we have shown localisation and clinical relevance of TGF-b1 activity levels in gastric cancer.

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“…MMP production is dramatically increased in OSCC, and study in our laboratory have previously shown that patients with tumors showing elevated activity of MMP-2 and MMP-9 had shorter disease-free survival period after treatment than patients with tumors exhibiting low MMP activities (41). Interestingly, previous reports demonstrated myofibroblasts as the main source of MMPs in fibrotic diseases (42,43) and some types of cancers (44)(45)(46). Furthermore, the observation that myofibroblasts may enhance the ability of cancer cells to invade is supported by the fact that in vitro the presence of MMPs secreted by myofibroblasts increased the invasion of cancer cells (47,48).…”

Section: Discussionmentioning

confidence: 99%

Isolation and characterization of myofibroblast cell lines from oral squamous cell carcinoma

Sobral

Zecchin²,

Aquino³

et al. 2011

Oncol Rep

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Abstract. Oral squamous cell carcinoma (OSCC) invasion is followed by several stromal events such as inflammatory and immune cell infiltration, neo-vascularization, fibroblast activation and occasionally myofibroblast emergence. Our previous studies demonstrated that myofibroblasts in the stroma of OSCC are associated with a more aggressive behavior, leading to shorter patient overall survival. Therefore, we evaluated whether OSCC-associated myofibroblasts have different characteristics compared to OSCC-associated fibroblasts. OSCC myofibroblast cell lines were isolated, cultured and characterized on the basis of the expression of specific isoform · of smooth muscle actin (·-SMA) and of the excessive production of type I collagen. To assess the proliferative potential of the cell lines, growth curves were constructed, whereas the production and activity of matrix metalloproteinases (MMP) were analyzed by ELISA and enzymography, respectively. Myofibroblast clones were positive for ·-SMA and vimentin, and negative for pan-cytokeratin and CD34. In long time cultures, Western blotting, flow cytometry and ELISA analysis revealed constant ·-SMA expression and elevated production of type I collagen. There were no differences on proliferative potential between fibroblast and myofibroblast clones, but myofibroblast cells secreted significantly higher levels of MMP-1, -2, -9 and -13. Furthermore, MMP-2 gelatinolytic activity was significantly higher in myofibroblast clones. The results of this study suggest that myofibroblasts may contribute to OSCC invasion through elevation of MMP synthesis.

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Overexpression of matrix metalloproteinase-2 mediates phenotypic transformation of lens epithelial cells

Cited by 42 publications

References 41 publications

RGTA OTR4120, a heparan sulfate mimetic, is a possible long‐term active agent to heal burned skin

RGTA OTR4120, a heparan sulfate mimetic, is a possible long‐term active agent to heal burned skin

Tissue level, activation and cellular localisation of TGF-β1 and association with survival in gastric cancer patients

Isolation and characterization of myofibroblast cell lines from oral squamous cell carcinoma

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