title: Expression of collagenases-1 and -3 and their inhibitors TIMP-1 and -3 correlates with the level of invasion in malignant melanomas.
abstract: Since proteolysis of the dermal collagenous matrix and basement membranes is required for local invasive growth and early metastasis formation of cutaneous melanomas, we have analysed the activities/expression levels of certain metalloproteinases in melanomas and cultured melanoma cells by in situ hybridization and Northern analysis. In addition to collagenases-1 and -3 that have been implicated in invasive growth behaviour of various malignant tumours, we analysed the levels of 72-kDa gelatinase and its activators MT1-MMP and TIMP-2 in cultured melanoma cells. The lesions examined included three cases of lentigo maligna and 28 cases of Clark grade I-V melanomas. The premalignant as well as the grade I tumours were consistently negative for collagenase-1 and -3 and TIMP-1 and -3. The collagenases were predominantly expressed in the cancer cells of Clark grade III and IV tumours. TIMP-1 and -3 were abundantly expressed in the cancer and/or stromal cells of grade III and IV melanomas, while TIMP-2 protein was detected also in melanomas representing lower invasive potential. Northern analysis of seven melanoma cell lines showed that the expression of collagenase-1 and TIMPs-1 and -3 was associated with 72-kDa gelatinase positivity. All melanoma cell lines were positive for MT1-MMP and TIMP-2 mRNAs. Our results suggest that overexpression of collagenases-1 and -3 and TIMPs-1 and -3 is induced during melanoma progression. Expression of TIMPs may reflect host response to tumour invasion in an effort to control MMP activity and preserve extracellular matrix integrity.
authors.affiliation: Department of Dermatology, Helsinki University Central Hospital, Finland.
authors.forename: K
authors.initials: K
authors.lastname: Airola
authors.forename: T
authors.initials: T
authors.lastname: Karonen
authors.forename: M
authors.initials: M
authors.lastname: Vaalamo
authors.forename: K
authors.initials: K
authors.lastname: Lehti
authors.forename: J
authors.initials: J
authors.lastname: Lohi
authors.forename: A L
authors.initials: AL
authors.lastname: Kariniemi
authors.forename: J
authors.initials: J
authors.lastname: Keski-Oja
authors.forename: U K
authors.initials: UK
authors.lastname: Saarialho-Kere
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015152:Blotting, Northern; D017364:Collagenases / Q000096:biosynthesis*; D018450:Disease Progression; D005260:Female; D005780:Gelatin; D018093:Gelatinases / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1; D053509:Matrix Metalloproteinase 13; D020778:Matrix Metalloproteinase 2; D061965:Matrix Metalloproteinase Inhibitors; D008545:Melanoma / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology*; D008666:Metalloendopeptidases / Q000096:biosynthesis / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis*; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D019715:Tissue Inhibitor of Metalloproteinase-1; D019717:Tissue Inhibitor of Metalloproteinase-3; D005780:Gelatin; D017364:Collagenases; D018093:Gelatinases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020781:Matrix Metalloproteinase 1