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.

Depletion of cell surface CD44 in nonmelanoma skin tumours is associated with increased expression of matrix metalloproteinase 7

“…The MMP‐9 antibody stained the dermal fibroblasts and glandular structures (Fig. 1b), in agreement with a previous report 11 . Staining of both MMP‐7 and MMP‐9 was localized diffusely in the cytoplasm (Figs 1 and 2).…”

Depletion of cell surface CD44 in nonmelanoma skin tumours is associated with increased expression of matrix metalloproteinase 7

“…The MMP‐9 antibody stained the dermal fibroblasts and glandular structures (Fig. 1b), in agreement with a previous report 11 . Staining of both MMP‐7 and MMP‐9 was localized diffusely in the cytoplasm (Figs 1 and 2).…”

Significance of matrix metalloproteinase-2 and matrix metalloproteinase-9 in nonmelanoma skin cancer

“…In concordance with the results of Kerkelä and Saarialho-Kere (2003) and Monhian et al (2005), in the present study normal skin samples showed weak MMP-2 reactivity in epidermal basal cells and focal MMP-9 reactivity scattered within the layers of the epidermis. Both MMP-2 and MMP-9 were focally weakly expressed in stromal and inflammatory cells.…”

“…Similar to the studies by Monhian et al (2005) and O'Grady et al (2007), we found no significant correlation between MMP-2 and MMP-9 expression and clinical variables such as age, sex, tumour location (sunexposed and non-sun-exposed) or diameter. Further studies are required to evaluate the exact relation between these variables and MMP expression.…”

Differential expression of stromal MMP-1, MMP-9 and TIMP-1 in basal cell carcinomas of immunosuppressed patients and controls

“…Collagenases cleave preferably various collagens but a number of other proteins as well [29]. MMP-1 is the major collagenolytic enzyme detected in BCC [47], and in this study, MMP-1 was detected in BCC epithelium and stromal cells in agreement with previous reports [38,46]. MMP-1 immunopositivity was significantly weaker in macrophages of the immunosuppressed, while fibroblasts tended to be more often immunopositive in the control group.…”

Depletion of cell surface CD44 in nonmelanoma skin tumours is associated with increased expression of matrix metalloproteinase 7

“…The MMP‐9 antibody stained the dermal fibroblasts and glandular structures (Fig. 1b), in agreement with a previous report 11 . Staining of both MMP‐7 and MMP‐9 was localized diffusely in the cytoplasm (Figs 1 and 2).…”

Significance of matrix metalloproteinase-2 and matrix metalloproteinase-9 in nonmelanoma skin cancer

“…In concordance with the results of Kerkelä and Saarialho-Kere (2003) and Monhian et al (2005), in the present study normal skin samples showed weak MMP-2 reactivity in epidermal basal cells and focal MMP-9 reactivity scattered within the layers of the epidermis. Both MMP-2 and MMP-9 were focally weakly expressed in stromal and inflammatory cells.…”

“…Similar to the studies by Monhian et al (2005) and O'Grady et al (2007), we found no significant correlation between MMP-2 and MMP-9 expression and clinical variables such as age, sex, tumour location (sunexposed and non-sun-exposed) or diameter. Further studies are required to evaluate the exact relation between these variables and MMP expression.…”

Differential expression of stromal MMP-1, MMP-9 and TIMP-1 in basal cell carcinomas of immunosuppressed patients and controls

“…Collagenases cleave preferably various collagens but a number of other proteins as well [29]. MMP-1 is the major collagenolytic enzyme detected in BCC [47], and in this study, MMP-1 was detected in BCC epithelium and stromal cells in agreement with previous reports [38,46]. MMP-1 immunopositivity was significantly weaker in macrophages of the immunosuppressed, while fibroblasts tended to be more often immunopositive in the control group.…”

Depletion of cell surface CD44 in nonmelanoma skin tumours is associated with increased expression of matrix metalloproteinase 7

“…The MMP‐9 antibody stained the dermal fibroblasts and glandular structures (Fig. 1b), in agreement with a previous report 11 . Staining of both MMP‐7 and MMP‐9 was localized diffusely in the cytoplasm (Figs 1 and 2).…”

Significance of matrix metalloproteinase-2 and matrix metalloproteinase-9 in nonmelanoma skin cancer

“…In concordance with the results of Kerkelä and Saarialho-Kere (2003) and Monhian et al (2005), in the present study normal skin samples showed weak MMP-2 reactivity in epidermal basal cells and focal MMP-9 reactivity scattered within the layers of the epidermis. Both MMP-2 and MMP-9 were focally weakly expressed in stromal and inflammatory cells.…”

“…Similar to the studies by Monhian et al (2005) and O'Grady et al (2007), we found no significant correlation between MMP-2 and MMP-9 expression and clinical variables such as age, sex, tumour location (sunexposed and non-sun-exposed) or diameter. Further studies are required to evaluate the exact relation between these variables and MMP expression.…”

Differential expression of stromal MMP-1, MMP-9 and TIMP-1 in basal cell carcinomas of immunosuppressed patients and controls

“…Collagenases cleave preferably various collagens but a number of other proteins as well [29]. MMP-1 is the major collagenolytic enzyme detected in BCC [47], and in this study, MMP-1 was detected in BCC epithelium and stromal cells in agreement with previous reports [38,46]. MMP-1 immunopositivity was significantly weaker in macrophages of the immunosuppressed, while fibroblasts tended to be more often immunopositive in the control group.…”