Expression and Regulation of MMP-20 in Human Tongue Carcinoma Cells

Väänänen, Antti; Srinivas, Ravi; Parikka, Mataleena; Palosaari, Heidi; Bartlett, John D.; Iwata, Kazushi; Grénman, Reidar; Stenman, Ulf‐Hǎkan; Sorsa, Timo; Salo, Tuula

doi:10.1177/00220345010800100501

Cited by 40 publications

(31 citation statements)

References 27 publications

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“…In support of this mechanism, radiotherapy increases the expression and activation of matrix metalloproteinases (MMPs) in various tissues (Araya et al, 2001;Strup-Perrot et al, 2006). To this end, we have shown that MMP-20, a type IV collagenase (Väänänen et al, 2001), is localized to the DEJ and that its processing is altered in teeth post-radiotherapy (McGuire et al, 2014a).…”

Section: Discussionmentioning

confidence: 82%

Type IV Collagen is a Novel DEJ Biomarker that is Reduced by Radiotherapy

McGuire¹,

Gorski

Dusevich³

et al. 2014

J Dent Res

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The dental basement membrane (BM) is composed of collagen types IV, VI, VII, and XVII, fibronectin, and laminin and plays an inductive role in epithelial-mesenchymal interactions during tooth development. The BM is degraded and removed during later-stage tooth morphogenesis; however, its original position defines the location of the dentinenamel junction (DEJ) in mature teeth. We recently demonstrated that type VII collagen is a novel component of the inner enamel organic matrix layer contiguous with the DEJ. Since it is frequently co-expressed with and forms functional complexes with type VII collagen, we hypothesized that type IV collagen should also be localized to the DEJ in mature human teeth. To identify collagen IV, we first evaluated defect-free erupted teeth from various donors. To investigate a possible stabilizing role, we also evaluated extracted teeth exposed to high-dose radiotherapy -teeth that manifest post-radiotherapy DEJ instability. We now show that type IV collagen is a component within the morphological DEJ of posterior and anterior teeth from individuals aged 18 to 80 yr. Confocal microscopy revealed that immunostained type IV collagen was restricted to the 5-to 10-µm-wide optical DEJ, while collagenase treatment or previous in vivo tooth-level exposure to > 60 Gray irradiation severely reduced immunoreactivity. This assignment was confirmed by Western blotting with whole-tooth crown and enamel extracts. Without reduction, type IV collagen contained macromolecular α-chains of 225 and 250 kDa. Compositionally, our results identify type IV collagen as the first macromolecular biomarker of the morphological DEJ of mature teeth. Given its network structure and propensity to stabilize the dermal-epidermal junction, we propose that a collagen-IV-enriched DEJ may, in part, explain its wellknown fracture toughness, crack propagation resistance, and stability. In contrast, loss of type IV collagen may represent a biochemical rationale for the DEJ instability observed following oral cancer radiotherapy.

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Section: Discussionmentioning

confidence: 82%

Type IV Collagen is a Novel DEJ Biomarker that is Reduced by Radiotherapy

McGuire¹,

Gorski

Dusevich³

et al. 2014

J Dent Res

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“…The following polyclonal antibodies were used in the immunohistochemical stainings: laminin-5 g2-chain (1 : 1000) (Pyke et al, 1995), (Hanemaaijer et al, 1997), MMP-9 (1 : 1000, Neomarkers, Fremont, CA, USA), MMP-20 (1 : 1000) (Väänänen et al, 2001), MMP-28 (1 : 500) (Lohi et al, 2001) and factor VIII (1 : 800, Dako A/S, Glostrup, Denmark). MMP-2 (1 : 2000, Suomen Bioanalytiikka, SBA, Turku, Finland), MMP-7 (1 : 80, Calbiochem, La Jolla, CA, USA), integrin avb6 (6.2G2 at 0.5 mg ml À1 (Weinreb et al, 2004), Biogen Idel, Inc., Cambridge, MA, USA), COX-2 (1 mg ml À1 , Cayman Chemical, Ann Arbor, Michigan, USA) and CD31 (1 : 30, DakoCytomation, Glostrup, Denmark) antibodies were monoclonal.…”

Section: Antibodiesmentioning

confidence: 99%

Collagenase-2 (matrix metalloproteinase-8) plays a protective role in tongue cancer

et al. 2008

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Squamous cell carcinoma (SCC) of the tongue is the most common cancer in the oral cavity and has a high mortality rate. A total of 90 mobile tongue SCC samples were analysed for Bryne's malignancy scores, microvascular density, and thickness of the SCC sections. In addition, the staining pattern of cyclooxygenase-2, avb6 integrin, the laminin-5 g2-chain, and matrix metalloproteinases (MMPs) -2, -7, -8, -9, -20, and -28 were analysed. The expression of MMP-8 (collagenase-2) was positively associated with improved survival of the patients and the tendency was particularly prominent in females. No sufficient evidence for a correlation with the clinical outcome was found for any other immunohistological marker. To test the protective role of MMP-8 in tongue carcinogenesis, MMP-8 knockout mice were used. MMP-8 deficient female mice developed tongue SCCs at a significantly higher incidence than wildtype mice exposed to carcinogen 4-Nitroquinoline-N-oxide. Consistently, oestrogen-induced MMP-8 expression in cultured HSC-3 tongue carcinoma cells, and MMP-8 cleaved oestrogen receptor (ER) a and b. According to these data, we propose that, contrary to the role of most proteases produced by human carcinomas, MMP-8 has a protective, probably oestrogen-related role in the growth of mobile tongue SCCs.

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“…It was demonstrated that MMP-20 was found to be expressed in oral squamous cell carcinoma (SCC) cells in vitro 196 but to date they are the only cells outside the tooth forming cells that have been shown to express MMP-20. In MMP-20 knock-out mice, an amelogenesis imperfecta phenotype was seen, but the circumpulpal dentine seemed apparently unaffected 23 .…”

Section: Growth Factorsmentioning

confidence: 99%