Differential patterns of stromelysin-2 (MMP-10) and MT1-MMP (MMP-14) expression in epithelial skin cancers.
Co-expression of several members of the matrix metalloproteinase (MMP) family is characteristic of human malignant tumours. To investigate the role of stromelysin-2 (MMP-10) in growth and invasion of skin tumours, we studied cutaneous carcinomas with high metastatic capacity (squamous cell carcinomas, SCCs), only locally destructive tumours (basal cell carcinomas, BCCs) and pre-malignant lesions (Bowen's disease and actinic keratosis) using in situ hybridization. Expression of MMP-10 was compared with that of stromelysin-1 (MMP-3) and of MT1-MMP, the expression of which has been shown to correlate with tumour invasiveness. MMP-10 was expressed in 13/21 SSCs and 11/19 BCCs only in epithelial laminin-5 positive cancer cells, while premalignant lesions were entirely negative. MT1-MMP mRNA was detected in 19/21 SCCs both in epithelial cancer cells and stromal fibroblasts and in 14/18 BCCs only in fibroblasts. The level of MMP-10 was upregulated in a cutaneous SCC cell line (UT-SCC-7) by transforming growth factor-alpha and keratinocyte growth factor, and by interferon-gamma in combination with transforming growth factor-beta1 and tumour necrosis factor-alpha both in UT-SCC-7 and HaCaT cells. Our results show that MMP-10 expression does not correlate with the invasive behaviour of tumours as assessed by their histology and MT1-MMP expression, but may be induced by the wound healing and inflammatory matrix remodelling events associated with skin tumours.
Department of Dermatology, Helsinki University Central Hospital, Helsinki, Finland.
E
E
Kerkelä
R
R
Ala-aho
J
J
Lohi
R
R
Grénman
V
V
M-Kähäri
U
U
Saarialho-Kere
D002280:Basal Cell Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D017403:In Situ Hybridization; D007642:Keratosis / Q000235:genetics / Q000378:metabolism; D053506:Matrix Metalloproteinase 10; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis / Q000235:genetics; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D000097794:Kalinin
D015815:Cell Adhesion Molecules; D006133:Growth Substances; D053506:Matrix Metalloproteinase 10; D019278:Matrix Metalloproteinase 3; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D012333:RNA, Messenger; D000097794:Kalinin