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Balance Between Activation and Inhibition of Matrix Metalloproteinase-2 (MMP-2) Is Altered in Colorectal Tumors Compared to Normal Colonic Epithelium

Digestive Diseases and Sciences volume 47, pages 1821–1830 (2002)Cite this article

Abstract

Matrix metalloproteinase-2 (MMP-2) is overexpressed in human cancers and facilitates tumor growth and metastasis. It is synthesized as an inactive proenzyme that is activated by membrane-type matrix metalloproteinase-1 (MT1-MMP) and inhibited by tissue inhibitor of metalloproteinase-2 (TIMP-2). We hypothesized that there is an imbalance between the expression of TIMP-2 and the expression of MMP-2 and MT1-MMP that favors activation of MMP-2 in malignant colon tumors compared to normal colonic tissue. Specimens of colon tumors and of adjacent normal mucosa were obtained from 22 patients at the time of surgical resection. MMP-2, MT1-MMP, and TIMP-2 RNA transcripts were measured in each sample using a quantitative reverse transcriptase polymerase chain reaction assay. We observed that MMP-2 RNA levels were significantly elevated in tumors compared to normal tissue (P = 0.039). In addition, the TIMP-2:MMP-2 ratio was twofold lower (P = 0.001) and the TIMP-2:MT1-MMP ratio was 1.5-fold lower (P = 0.003) in tumors compared to normal mucosa. These results suggest that the balance between genes that activate and inhibit MMP-2 is shifted toward activation in colon tumors. The abnormal expression of gene products that regulate MMP-2 activity may be an important early step in the malignant transformation of colon cancer and may provide a useful target for new chemoprevention and adjuvant treatment strategies.

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  1. Dartmouth Medical School, Hanover, New Hampshire, USA

    Deborah L. Ornstein

  2. Veterans Administration Medical Center, White River Junction, Vermont, USA

    Kenneth H. Cohn

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Ornstein, D.L., Cohn, K.H. Balance Between Activation and Inhibition of Matrix Metalloproteinase-2 (MMP-2) Is Altered in Colorectal Tumors Compared to Normal Colonic Epithelium. Dig Dis Sci 47, 1821–1830 (2002). https://doi.org/10.1023/A:1016456914723

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  • DOI: https://doi.org/10.1023/A:1016456914723

  • colorectal cancer
  • matrix metalloproteinases
  • malignant transformation
  • metastasis