Comparative Analysis of the Expression Patterns of Metalloproteinases and Their Inhibitors in Breast Neoplasia, Sporadic Colorectal Neoplasia, Pulmonary Carcinomas and Malignant non-Hodgkin's Lymphomas in Humans

Br J Cancer. 1996 Jun;73(11):1401-8. doi: 10.1038/bjc.1996.266.

Abstract

Matrix metalloproteinases (MMPs) and their inhibitors (tissue inhibitors of metalloproteinases, TIMPs) play essential roles in the remodelling of the extracellular matrix (ECM). Results of in vivo and in vitro studies suggest that the balance between MMPs and TIMPs is altered in neoplasia, contributing to the invasive and metastatic properties of malignant tumours. In this study we have analysed the expression of five MMP genes and TIMP-1 and TIMP-2 in 37 benign and malignant lesions of human breast using Northern blot analysis. MMP-9 (92 kDa gelatinase) and MMP-11 (stromelysin 3) were most consistently expressed by carcinomas. Based on detection of either MMP-9 or MMP-11 mRNAs, we were able to distinguish between malignant and benign disease with a predictive accuracy of 90% with 94% sensitivity and 85% specificity. Subsequently, these results were compared with results for carcinomas of colon and lung and malignant non-Hodgkin's lymphomas (NHL). Elevated MMP-9 and TIMP-1 expression was observed in all four systems. MMP-11 characterised all carcinomas as well as carcinomas in situ but was not detectable in NHL. Our data therefore argue that there are remarkably similar patterns of specific functions involved in ECM remodelling that correlate with malignancy in different human tumours of different histogenesis. However, MMP-11 expression is a characteristic of tumours of epithelial origin that is not found in lymphoid neoplasia. Thus it suggests that MMP-11 may play a regulatory role in the invasion and metastasis of carcinomas.

Publication types

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

MeSH terms

  • Adenofibroma / metabolism
  • Adenofibroma / pathology
  • Biomarkers, Tumor / analysis*
  • Breast / cytology
  • Breast / metabolism
  • Breast / pathology
  • Breast Diseases / metabolism
  • Breast Diseases / pathology
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • Female
  • Fibrocystic Breast Disease / metabolism
  • Fibrocystic Breast Disease / pathology
  • Gelatinases / biosynthesis
  • Glycoproteins / analysis
  • Glycoproteins / biosynthesis*
  • Humans
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Lymphoma, Non-Hodgkin / metabolism
  • Lymphoma, Non-Hodgkin / pathology*
  • Matrix Metalloproteinase 11
  • Metalloendopeptidases / analysis
  • Metalloendopeptidases / biosynthesis*
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Predictive Value of Tests
  • Protein Biosynthesis*
  • Proteins / analysis
  • RNA, Messenger / analysis
  • RNA, Messenger / biosynthesis
  • Sensitivity and Specificity
  • Tissue Inhibitor of Metalloproteinase-2
  • Tissue Inhibitor of Metalloproteinases
  • Transcription, Genetic*

Substances

  • Biomarkers, Tumor
  • Glycoproteins
  • Proteins
  • RNA, Messenger
  • Tissue Inhibitor of Metalloproteinases
  • Tissue Inhibitor of Metalloproteinase-2
  • Gelatinases
  • Matrix Metalloproteinase 11
  • Metalloendopeptidases