Role of matrix metalloproteinase‐9 in progression of mouse skin carcinogenesis

Papathoma, Alexandra; Zoumpourlis, Vassilios; Balmain, Allan; Pintzas, Alexander

doi:10.1002/mc.1042

Cited by 29 publications

(20 citation statements)

References 30 publications

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“…The promoter elements of GM-CSF, MMP-9 and MMP-3 bind different AP-1 complexes in a selective manner (Szabowski et al, 2000;Hulboy et al, 2001;Papathoma et al, 2001). The present study shows that TNFR1 and TNFR2 can regulate multiple c-Jun containing AP-1 complexes, since differential expression of GM-CSF, MMP-9 and MMP-3 was observed in TNFR1 À/À compared to TNFR2 À/À .…”

Section: Discussionmentioning

confidence: 99%

Expression of both TNF-α receptor subtypes is essential for optimal skin tumour development

et al. 2003

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Keratinocyte-derived TNF-a acts as an endogenous tumour promoter and can also regulate AP-1 activity in mouse epidermis. To gain further insight into TNF-a signalling during skin tumour formation, mice deficient in TNFR1 (TNFR1 À/À mice) or TNFR2 (TNFR2 À/À mice) were subjected to chemical carcinogenesis. Tumour multiplicity was significantly reduced in TNFR1 À/À and TNFR2 À/À mice compared to wild-type (wt) mice, suggesting that both receptors have protumour activity. However, TNFR1 À/À mice were markedly more resistant to tumour development than TNFR2 À/À mice indicating that TNFR1 is the major mediator of TNF-a-induced tumour formation. TNFR1 and TNFR2 were both expressed in wt epidermis during tumour promotion and by primary keratinocytes in vitro. TPA-induced c-Jun expression was transient in TNFR1 À/À and TNFR2 À/À compared to wt epidermis and this was reflected by reduced induction of the AP-1-responsive genes granulocyte/macrophage-colony stimulating factor, matrix metalloproteinase-9 and matrix metalloproteinase-3. These genes were differentially regulated in TNFR1 À/À compared to TNFR2 À/À epidermis, suggesting that the TNF-a receptors act independently via different AP-1 complexes to transduce TNF-a signals during tumour promotion. In addition, TNFR2 cooperated with TNFR1 to optimise TNFR1-mediated TNF-a bioactivity on keratinocytes in vitro. Our data provide further insight into TNF-a signalling in malignancy and provide some rationale for the use of TNF-a antagonists in the treatment of cancer.

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Section: Discussionmentioning

confidence: 99%

Expression of both TNF-α receptor subtypes is essential for optimal skin tumour development

et al. 2003

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“…MMP-9 is expressed by normal keratinocytes (Han et al, 2001;Kobayashi et al, 2001) and is induced in migrating keratinocytes following wounding in vitro (McCawley et al, 1998) and in vivo (Lund et al, 1999;Mohan et al, 2002). Transformed keratinocytes and SCC also express MMP-9 (Papathoma et al, 2001;Thomas et al, 2001a). MMP-9 has been extensively studied in many human and murine cancers due to its potential role in tumour invasion and metastasis (Naylor et al, 1994;Liabakk et al, 1996;Hanemaaijer et al, 2000;Scott et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

TNF-α regulates epithelial expression of MMP-9 and integrin αvβ6 during tumour promotion. A role for TNF-α in keratinocyte migration?

et al. 2004

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Mice deficient in TNF-a (TNF-a À/À mice) are resistant to skin carcinogenesis and expression of MMP-9 is inhibited in TNF-a À/À mice during skin tumour development. In the early stages of tumour promotion, MMP-9 protein initially localized to the follicular epidermis but subsequently began to accumulate in the interfollicular epidermis of wild-type but not TNF-a À/À mice. Inhibition of TNF-a or MMP-9 function reduced keratinocyte migration in vitro. In addition, a deficiency of TNF-a delayed re-epithelialization in vivo and this correlated with reduced MMP-9 expression. Collectively, these data suggest that MMP-9 regulates keratinocyte migration in a TNF-a-dependent manner. Expression profiling of genes that control cell adhesion and migration revealed markedly lower levels of the integrin subunits av and b6 in TNF-a À/À compared with wild-type keratinocytes in vitro. avb6 expression was upregulated by keratinocytes in vitro and during tumour promotion in vivo in a TNF-adependent manner. Furthermore, avb6 blockade significantly inhibited keratinocyte migration and TNFa-stimulated MMP-9 expression in vitro. These data illustrate a novel TNF-a-dependent mechanism for the control of avb6 expression and suggest one pathway for TNF-a regulation of MMP-9. Increased MMP-9 and avb6 expression may stimulate epithelial cell migration during tumour formation and may be one mechanism whereby TNF-a acts as an endogenous tumour promoter.

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“…An increased expression of MMP-9 during the progression of carcinogenesis, and decreased tumor metastasis in MMP-9-deficient mice have been reported 43,44 . These findings suggested that MMP-9 is a crucial factor for the progression of carcinogenesis and metastasis.…”

Section: Discussionmentioning

confidence: 99%

The Increased Expression of Matrix Metalloproteinase-9 Messenger RNA in the Non-lesional Skin of Patients with Large Plaque Psoriasis Vulgaris

Lee

Lew

2009

Ann Dermatol

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Background:A difference of the interleukin-18 (IL-18) mRNA expression among several proinflammatory genes was previously observed between large plaque (LP) psoriasis patients (more than 5 cm lesions are typical) and small plaque (SP) psoriasis patients (1∼2 cm lesions are typical). Therefore, it is necessary to test whether there is any difference in the expression of the genes that activate IL-18 or the expression of genes that are induced by IL-18. Objective: To test the differential mRNA expressions of caspase-1, STAT-6, MMP-1, MMP-2, MMP-9 and TIMP-1 according to the clinical types of psoriasis vulgaris lesions in Korean patients, we have analyzed the skin samples of psoriasis vulgaris patients. Methods: The total cellular RNA of skin samples from groups of patient with LP and SP psoriasis was analyzed by performing real-time PCR (the Taqman method) to compare the differences in the mRNA expressions. Results: The caspase-1 and STAT-6 mRNA expression levels from the SP lesional skin of the patients were increased compared with the caspase-1 and STAT-6 mRNA expression levels from SP non-lesional skin or normal skin, but these expression levels from the SP non-lesional skin were not significantly different from those of the LP non-lesional skin. Among MMP-1, MMP-2, MMP-9 and TIMP-1, the expressions of MMP-1, MMP-2 and MMP-9 mRNA were increased in the SP lesional skin compared with those of the SP non-lesional skin. The MMP-1 mRNA expressions in both the LP and SP lesional skin were increased compared with those in the normal skin (p=0.028 and p=0.007 respectively). The MMP-9 mRNA expression in the LP non-lesional skin was elevated compared with the MMP-9 mRNA expression in the SP non-lesional skin (p=0.047). The TIMP-1 mRNA expression levels from the non-lesional skin and the lesional skin of the psoriasis patients and the normal skin samples were not significantly different. Conclusion: The increased expression of MMP-9 mRNA in the LP non-lesional skin compared to that of the SP non-lesional skin in the psoriatic skin suggests that the increased MMP-9 mRNA expression is related to the large size type of lesion.

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Role of matrix metalloproteinase‐9 in progression of mouse skin carcinogenesis

Cited by 29 publications

References 30 publications

Expression of both TNF-α receptor subtypes is essential for optimal skin tumour development

Expression of both TNF-α receptor subtypes is essential for optimal skin tumour development

TNF-α regulates epithelial expression of MMP-9 and integrin αvβ6 during tumour promotion. A role for TNF-α in keratinocyte migration?

The Increased Expression of Matrix Metalloproteinase-9 Messenger RNA in the Non-lesional Skin of Patients with Large Plaque Psoriasis Vulgaris

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