Matrix metalloproteinase-19 is expressed by proliferating epithelium but disappears with neoplastic dedifferentiation.
MMP-19 (also designated RASI) is a recently discovered member of a large family of zinc-dependent proteolytic enzymes, most of which have been implicated in cancer growth and metastasis. It differs from the others by its chromosomal location and structure and is expressed by endothelial and vascular smooth muscle cells in vivo. Our aim was to study the putative role of MMP-19 in skin cancer. We also examined its regulation in keratinocyte cultures using quantitative TaqMan RT-PCR. Our results show that MMP-19 can also be detected in stimulated keratinocytes by Northern and Western analyses. In wounds, it was found in keratinocytes outside the migrating area, while in BCC and SCC, it was present in the hyperproliferative (p63-positive), E-cadherin-negative epidermis at the tumor surface but downregulated in invasive cancer islands. Expression was also evident in endothelial cells of neoangiogenic regions and in occasional stromal fibroblasts. Of the 12 tested cytokines/growth factors, only TNF-alpha and PMA were able to stimulate the expression of MMP-19 mRNA in primary keratinocytes. No MMP-19 mRNA was detected by Northern analysis in cultured HaCaT or A5 cells or in an SCC cell line established from head-and-neck cancer. Our data suggest that, unlike most MMPs, MMP-19 expression in the epidermis is downregulated during transformation and histologic dedifferentiation.
Impola
Ulla
U
Department of Dermatology, Helsinki University Central Hospital and Biomedicum Helsinki, Helsinki, Finland.
Toriseva
Mervi
M
Suomela
Sari
S
Jeskanen
Leila
L
Hieta
Niina
N
Jahkola
Tiina
T
Grenman
Reidar
R
Kähäri
Veli-Matti
VM
Saarialho-Kere
Ulpu
U
D015152:Blotting, Northern; D015153:Blotting, Western; D002280:Basal Cell Carcinoma / Q000201:enzymology* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000473:pathology; D002454:Cell Differentiation; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D015536:Down-Regulation; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D007124:Immunoenzyme Techniques; D015603:Keratinocytes / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D053505:Matrix Metalloproteinases, Secreted; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D012878:Skin Neoplasms / Q000201:enzymology* / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D053505:Matrix Metalloproteinases, Secreted; D008666:Metalloendopeptidases; C108362:matrix metalloproteinase 19; D013755:Tetradecanoylphorbol Acetate