Immunolocalizations of human gelatinase (type IV collagenase, MMP-9) and TIMP (tissue inhibitor of metalloproteinases) in normal epidermis and some epidermal tumors

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.

Differential Regulation of MMP-2 and MMP-9 Gelatinases in Cultured Human Keratinocytes

“…MMP-9, also known as gelatinase B [2] or 92-kD type IV collagenase [3, 4], is secreted by keratinocytes [3, 16, 17], polymorphonuclear leukocytes [5, 29] and tumor cell lines such as SV-40 transformed human lung fibroblasts [4] and HT1080 fibrosarcoma cells [6]. MMP-2, also known as gelatinase A [2] or 72-kD type IV collagenase [10, 12], is secreted by fibroblasts [5] and tumor cell lines such as H- ras oncogene transformed human bronchial epithelial cells [10].…”

“…In vitro studies suggest that two kinds of gelatinase (a 72-kD enzyme termed MMP-2 and a 92-kD form termed MMP-9) play important roles as key enzymes in tissue metabolism [3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17], although their specific roles in vivo are still unknown. We have previously demonstrated the existence of MMP-9 gelatinase in the granular layer of the epidermis and in dyskeratotic cells of lesions of Bowen’s disease and Hailey-Hailey disease [6, 7]. In these immunohistochemical studies we used monoclonal antibodies against MMP-9 derived from human polymorphonuclear leukocytes [5].…”

Expression of matrix metalloproteinase-1, -9, -13, and tissue inhibitor of metalloproteinases-1 in basal cell carcinomas of the eyelid

“…MMPs, particularly MMP-1, were reported to be the major collagenolytic enzyme responsible for collagen damage in UV-irradiated human skin [10]. Moreover, MMP-1-, MMP-9-, and MMP-13-expression was shown to be involved in the degradation of extracellular matrix and subsequent tumor invasion in head and neck squamous cell carcinomas and BCCs [7,[10][11][12][13][14]. This made exactly these enzymes excellent candidates for our investigations.…”

“…However, no overall consistent pattern of MMP expression across a variety of types of human cancer has been identified, and the selective role of protease families in specific tumors is unknown. MMP up-regulation has been reported in UV-irradiated human skin [10] and skin cancers including squamous cell carcinomas [11][12][13][14], Bowen's disease [14], and basal cell carcinomas [12,[15][16][17]. The aim of the present study was to evaluate the expression of matrix metalloproteinase (MMP) -1, -9, -13 and tissue inhibitor of metalloproteinases (TIMP) -1 in tumor epithelial cells and surrounding stroma in primary basal cell carcinomas of the eyelid, and to assess their role as prognostic markers for tumor recurrence.…”

A Case of Anaphylactoid Purpura with Multiple Blister Formation: Possible Pathophysiological Role of Gelatinase (MMP-9)

“…Zymography, using sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis (PAGE) with gelatin was performed as previously reported [2, 3] on the blister fluid and the patient’s plasma together with purified human PMN gelatinase [4] and conditioned culture media from fibroblasts [5] and keratinocytes [6]. Briefly, samples were solubilized in 0.05 M Tris-HCl, pH 7.4, 5 m M CaCl 2 , 1% SDS, 5% glycerol and separated on 7.5% SDS-PAGE gels containing 0.5% gelatin.…”