Transformation-specific matrix metalloproteinases (MMP)-7 and MMP-13 are expressed by tumour cells in epidermolysis bullosa-associated squamous cell carcinomas

Abstract

These results identify MMP-7 and MMP-13 as tumour cell-specific markers for SCC progression and as potential therapeutic targets in RDEB-associated SCC. The pattern of immunolabelling suggests that MMP-7 may shed E-cadherin and syndecan-1 from the SCC cell surface.

Genetic Predisposition to Cutaneous Squamous Cell Carcinoma

“…In support of this notion, recent observations by a separate group did not find a correlation between RDEB disease severity and MMP1 genotype (Kern et al, 2009). MMP protein expression has been investigated in RDEB cSCC: MMP-7 protein levels were detected in both RDEB SCC (25 of 25 samples) and UV induced cSCC (60 of 61 samples) but only detected in 1 of 27 normal skin samples (Kivisaari et al, 2008). The intensity of MMP-7 immunostaining was correlated significantly and positively with the histological grade of RDEB SCC tumour, which was not observed in sporadic UV-induced cSCC.…”

Serpin Peptidase Inhibitor Clade A Member 1 (SerpinA1) Is a Novel Biomarker for Progression of Cutaneous Squamous Cell Carcinoma

“…[1][2][3][4] At present, only a few specific biomarkers for cutaneous SCC have been identified, including STAT3, 44 E-cadherin, 45 and matrix metalloproteinases 13, 46 12, 47 and 7. 6,48 SerpinA1 has been previously suggested as a biomarker for the progression of insulinoma 49 and thyroid cancer. 50 In this study, we introduced SerpinA1 as a potential biomarker for the progression of cutaneous SCCs combined with other biomarkers mentioned previously herein.…”

“…6,25 Mouse Skin Chemical Carcinogenesis Normal (n ϭ 5), acetone-treated (n ϭ 2), and hyperplastic skin (n ϭ 6) and SCC (n ϭ 17) samples were collected from skin of FVB/N HanHsd mice (maintained at the Laboratory Animal Centre, University of Oulu, Oulu, Finland). Mouse skin carcinogenesis was induced as previously described.…”

“…6,25 To enhance the comparability and reliability of the IHC analysis results, we used an automated immunostaining device and the tissue microarray (TMA) technique. TMA blocks were generated from the original paraffin blocks using a tissue arrayer (Beecher Instruments Inc., Sun Prairie, WI), as previously described.…”

“…[1][2][3] An example of the latter is individuals with recessive dystrophic epidermolysis bullosa (RDEB), who often develop rapidly progressing cutaneous SCCs at sites of chronic ulceration and scarring. 5,6 At present, no specific molecular markers for progression of cutaneous SCC are available. Such biomarkers would be valuable in clinical practice for early detection of individual cutaneous SCCs with a high risk of progression and metastasis.…”