Differential patterns of stromelysin-2 (MMP-10) and MT1-MMP (MMP-14) expression in epithelial skin cancers

Br J Cancer. 2001 Mar 2;84(5):659-69. doi: 10.1054/bjoc.2000.1634.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Basal Cell / genetics*
  • Carcinoma, Basal Cell / metabolism
  • Carcinoma, Basal Cell / pathology
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Cell Adhesion Molecules / metabolism
  • Fibroblasts / metabolism
  • Growth Substances / pharmacology
  • Humans
  • In Situ Hybridization
  • Keratosis / genetics
  • Keratosis / metabolism
  • Matrix Metalloproteinase 10
  • Matrix Metalloproteinase 3 / biosynthesis
  • Matrix Metalloproteinase 3 / genetics
  • Matrix Metalloproteinases, Membrane-Associated
  • Metalloendopeptidases / biosynthesis
  • Metalloendopeptidases / genetics*
  • RNA, Messenger / biosynthesis
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology
  • Transcription, Genetic
  • Transcriptional Activation
  • Tumor Cells, Cultured

Substances

  • Cell Adhesion Molecules
  • Growth Substances
  • RNA, Messenger
  • kalinin
  • Matrix Metalloproteinases, Membrane-Associated
  • Metalloendopeptidases
  • Matrix Metalloproteinase 3
  • Matrix Metalloproteinase 10