Matrix Metalloproteinase Expression in Normal Skin Associated With Basal Cell Carcinoma and in Distal Skin From the Same Patients

Abstract

To obviate the difficulty of ruling out confounding variables (eg, age, individual variability) as the source of differences seen when comparing tumor tissue and control tissue from unrelated individuals, we examined the expression of matrix metalloproteinase (MMP)-1 (interstitial collagenase) and MMP-9 (92-kDa gelatinase B) in histologically normal skin immediately adjacent to basal cell carcinomas (peritumoral tissue) after Mohs micrographic surgery and postauricular skin from the same patients. Design: Peritumoral and postauricular skin samples were obtained from 17 patients undergoing Mohs surgery. Expression of MMP-1 and MMP-9 was examined in these specimens using a combination of approaches including zymography, collagen-degradation assays, and immunohistology. Results: The expression levels of MMP-1 and MMP-9 were consistently elevated in the peritumoral tissue compared with skin from the distal site. Conclusion: This finding indicates that even when potentially important variables such as age and individual variability are controlled for, tumor-specific effects on the expression of MMP-9 and MMP-1 remain.

Vascular tube formation on matrix metalloproteinase-1-damaged collagen

“…Consistent with past reports (Varani et al, 2000(Varani et al, , 2001(Varani et al, , 2002Brennan et al, 2003;Monhian et al, 2005;Yucel et al, 2005), the 3 4 -and 1 4 -sized fragments that are the principal products of interstitial collagenase digestion of type I collagen were the predominant species identified. Not surprisingly, as significant amounts of active MMP-2 and MMP-9 (as well as other enzymes) are also present in skin organ culture fluid, fragments of other sizes were also detected.…”

“…In the skin, both basal epithelial tumours and squamous epithelial tumours produce a large amount of tissue damage. Collagen destruction is visible ultrastructurally and biochemically in these tumours (Monhian et al, 2005;Yucel et al, 2005), and new vessels are prominent in the partially degraded connective tissue. In past studies from our laboratory, we showed that the epithelial tumour cells themselves, but especially the surrounding fibroblasts, produce large amounts of MMP-1.…”

“…Culture fluids from several tissues were 'pooled', aliquoted and stored at À801C. Our previous studies have characterised the profile of MMPs in organ culture fluid from basal cell tumours (Varani et al, 2000;Monhian et al, 2005;Yucel et al, 2005). The culture fluids contain a large amount of active MMP-1 but virtually no MMP-8 (neutrophil collagenase) or MMP-13 (collagenase-3).…”

Overexpression of matrix metalloproteinase 1 in dermal fibroblasts from DNA repair-deficient/cancer-prone xeroderma pigmentosum group C patients

“…BCCs virtually never lead to metastasis whereas SCCs do at a significant rate (10 À2 ). In the case of BCCs, MMP1 seems to be overexpressed solely in stromal cells surrounding the tumor (Monhian et al, 2005). In the case of SCCs, high amount of MMP1 mRNA has been detected in both the tumor and surrounding stromal cells, a pattern that could contribute to the significant metastatic potential of SCCs compared to BCCs (Gray et al, 1992;Tsukifuji et al, 1999).…”

Expressão de metaloproteinases de matriz e de seus inibidores teciduais em carcinomas basocelulares

“…Na epiderme não-neoplásica, a expressão de MMP e TIMP foi freqüentemente identificada nos queratinócitos das camadas basais. Esses achados têm sido descritos por outros autores em epiderme de pele não-associada à neoplasia, fato que tem sido interpretado como expressão antigênica constitutiva (17,23) . Assim, e considerando-se que o CBC apresenta caracteristicamente diferenciação semelhante às células localizadas na camada basal do epitélio, optamos por enfatizar a avaliação dessas enzimas no parênquima neoplásico, diferentemente da maioria dos estudos anteriores, que optaram por investigar exclusivamente a sua expressão em fibroblastos estromais.…”