Abstract
The matrix metalloproteinases (MMPs) MMP-2 and MMP-9 (gelatinases) have been suggested as serving an important role in cleaving the basement membrane structure. Tissue inhibitors of metalloproteinases TIMPs (particularly TIMP-1) are known to inhibit MMPs. Based on this background, we raised monoclonal antibodies against human gelatinase (MMP-9) and human recombinant TIMP (TIMP-1), and immunostained these two components in skin from patients with squamous cell carcinoma (SCC), Bowen's disease (BD) and keratoacanthoma (KA). MMP-9 showed positive staining mainly in the granular layer of normal epidermis. In some cases of SCC and BD, MMP-9 showed positive staining in the dysplastic lesions even in the basal layer. TIMP showed a thorough positivity in normal epidermis. Unstained regions with this antibody were observed in SCC and BD. These results suggest that an altered staining pattern for MMP-9 and TIMP may be closely related to the malignant transformation of SCC and BD.
Similar content being viewed by others
References
Adams JC, Watt FM (1990) Changes in keratinocyte adhesion during terminal differentiation: reduction in fibronectin binding precedes α5β1 integrin loss from the cell surface, Cell 63:425–435
Bertaux B, Hornebeck W, Eisen AZ, Dubertret L (1991) Growth stimulation of human keratinocytes by tissue inhibitor of metalloproteinases. J Invest Dermatol 97:679–685
Carter WG, Ryan MC, Gahr PJ (1991) Epiligrin, a new cell adhesion ligand for integrin α3β1 in epithelial basement membranes Cell 65:599–610
Collier JE, Wilhelm SM, Eisen AZ, Marmer BL, Grant GA, Seltzer JL, Kronberger A, He C, Bauer EA, Goldberg GI (1988) H-ras oncogene-transformed human bronchial epithelial cells (TBE-1) secrete a single metalloprotease capable of degrading basement membrane collagen. J Biol Chem 263:6579–6587
Goldberg GI, Strongin A, Collier IE, Genrich LT, Marmer BL (1992) Interaction of 92-kDa type IV collagenase with the tissue inhibitor of metalloproteinases prevents dimerization, complex formation with interstitial collagenase, and activation of the proenzyme with stromelysin. J Biol Chem 267:4583–4591
Green H (1977) Terminal differentiation of cultured human epidermal cells. Cell 11:405–416
Karelina TV, Hruza GJ, Goldberg GI, Eisen AZ (1993) Localization of 92-kDa type IV collagenase in human skin tumors: comparison with normal human fetal and adult skin. J Invest Dermatol 100:159–165
Kjeldsen L, Bjerrum OW, Hovgaard D, Johnsen AH, Sehested M, Borregaard N (1992) Human neutrophil gelatinase: A marker for circulating blood neutropils. Purification and quantitation by enzyme linked immunosorbent assay. Eur J Haematol 49: 180–191
Kleiner DE Jr, Stetler-Stevenson WG (1993) Structural biochemistry and activation of matrix metalloproteinases. Curr Opin Cell Biol 5:891–897
Kobayashi T, Hori H, Kanamori T, Hattori S, Takagi T, Watanabe H, Nishikawa T, Nagai Y (1993) Monoclonal antibodies to human polymorphonuclear leukocyte gelatinase (type IV collagenase) are cross-reactive with fibroblast gelatinase. Biochem Biophys Res Commun 193:490–496
Kubota S, Mitsudomi T, Yamada Y (1991) Invasive human fibrosarcoma DNA mediated induction of a 92kDa gelatinase/type IV collagenase leads to an invasive, phenotype. Biochem Biophys Res Commun 181:1539–1547
Levy AT, Cioce V, Sobel ME, Garbisa S, Grigioni WF, Liotta LA, Stetler-Stevenson WG (1991) Increased expression of the Mr 72,000 type IV collagenase in human colonic adenocarcinoma. Cancer Res 51:439–444
Matrisian LM (1990) Metalloproteinases and their inhibitors in matrix remodeling. Trends Genet 6:121–125
Mauch C, Krieg T, Bauer EA (1994) Role of the extracellular matrix in the degradation of connective tissue. Arch Dermatol Res 287:107–114
McCall CA, Cohen JJ (1991) Programmed cell death in terminally differentiating keratinocytes: role of endogenous endonuclease. J Invest Dermatol 97:111–114
Miyazaki K, Hasegawa M, Funahashi K, Umeda M (1993) A metalloproteinase inhibitor domain in Alzheimer amyloid protein precursor. Nature 362:839–841
Monteagudo C, Merino MJ, San-Juan J, Liotta LA, Setler-Stevenson WG (1990) Immunohistochemical distribution of type IV collagenase in normal, benign, and malignant breast tissue. Am J Pathol 136:585–592
Oishi M, Maeda K, Sugiyama S (1994) Distribution of apoptosis-mediating Fas antigen in human skin and effects of anti-Fas monoclonal antibody on human epidermal keratinocyte and squamous cell carcinoma cell lines. Arch Dermatol Res 286: 396–407
Okada Y, Gonoji Y, Nakanishi I, Nagase H, Hayakawa T (1990) Immunohistochemical demonstration of collagenase and tissue inhibitor of metalloproteinases (TIMP) in synovial lining cells of rheumatoid synovium. Virchows Archiv B Cell Pathol 59:305–312
Okada Y, Gonoji Y, Naka K, Tomita K, Nakanishi I, Iwata K, Yamashita K, Hayakawa T (1992) Matrix metalloproteinase 9 (92-kDa gelatinase/type IV collagenase) from HT 1080 human fibrosarcoma cells. Purification and activation of the precursor and enzymic properties. J Biol Chem 267:21712–21719
Pyke C, Ralfkiaer E, Huhtala P, Hurskainen T, Danø K, Tryggvason K (1992) Localization of messenger RNA for Mr 72,000 and 92,000 type IV collagenases in human skin cancers by in situ hybridization. Cancer Res 52:1336–1341
Sarret Y, Woodley DT, Goldberg GS, Kronberger A, Wynn KC (1992) Constitutive synthesis of a 92 kDa keratinocyte-derived type IV collagenase is enhanced by type I collagen and decreased by type IV collagen matrices. J Invest Dermatol 99: 836–841
Sato H, Kida Y, Mai M, Endo Y, Sasaki T, Tanaka J, Seiki M (1992) Expression of genes encoding type IV collagen-degrading metalloproteinases and tissue inhibitors of metalloproteinases in various human tumor cells. Oncogene 7:77–83
Sayama K, Yonehara S, Watanabe Y, Miki Y (1994) Expression of Fas antigen on keratinocytes in vivo and induction of apoptosis in cultured keratinocytes. J Invest Dermatol 103: 330–334
Schroeder WT, Thacher SM, Stewart-Geletka S, Annarella M, Chema D, Siciliano MJ, Davies PJA, Tang HY, Sowa BA, Duvic M (1992) Type I keratinocyte transglutaminase: expression in human skin and psoriasis. J Invest Dermatol 99:27–34
Spandau DF (1994) Distinct conformations of p53 are observed at different stages of keratinocyte differentiation. Oncogene 9: 1861–1868
St»hle-Bäckdahl M, Parks WC (1993) 92-kd gelatinase is actively expressed by eosinophils and stored by neutrophils in squamous cell carcinoma. Am J Pathol 142:995–1000
Tamada Y, Takama H, Kitamura T, Yokochi K, Nitta Y, Ikeya T, Matsumoto Y (1994) Identification of programmed cell death in normal human skin tissues by using specific labelling of fragmented DNA. Br J Dermatol 131:521–524
Tokimitsu I, Ohyama K, Tajima S, Nishikawa T (1991) Secretion of a unique collagen by spontaneously transformed murine keratinocytes (PAM cells) in vitro. J Invest Dermatol 96:267–272
Uría JA, Ferrando AA, Velasco G, Freije JM, López-Otín C (1994) Structure and expression in breast tumors of human TIMP-3, a new member of the metalloproteinase inhibitor family. Cancer Res 54:2091–2094
Wilhelm SM, Collier IE, Marmer BL, Eisen AZ, Grant GA, Goldberg GI (1989) SV40-transformed human lung fibroblasts secrete a 92-kDa type IV collagenase which is identical to that secreted by normal human macrophages. J Biol Chem 264: 17213–17221
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kobayashi, T., Onoda, N., Takagi, T. et al. Immunolocalizations of human gelatinase (type IV collagenase, MMP-9) and TIMP (tissue inhibitor of metalloproteinases) in normal epidermis and some epidermal tumors. Arch Dermatol Res 288, 239–244 (1996). https://doi.org/10.1007/BF02530091
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF02530091