Matrix metalloproteinase-2 expression in stromal tissues is a consistent prognostic factor in stage II colon cancer

Cancer Sci. 2009 May;100(5):852-8. doi: 10.1111/j.1349-7006.2009.01116.x.


For patients with stage II colon cancer, the usefulness of adjuvant chemotherapy remains controversial. Therefore, it is important to identify high-risk indicators. The biological prognostic factors for recurrence might allow further insight into the optimal treatment strategy for patients with node-negative disease. Matrix metalloproteinase-2 seems to be one of the essential factors for tumor invasion and lymph node metastasis. In this study, we analyzed the expression of cyclooxygenase-2 and matrix metalloproteinase-2 by immunohistochemical staining in 109 patients with stage II colon cancer. A positive correlation was observed between tumor cyclooxygenase-2 and tumor matrix metalloproteinase-2 expression (P = 0.0006) and between tumor cyclooxygenase-2 and stromal matrix metalloproteinase-2 expression (P < 0.0001). Stromal matrix metalloproteinase-2 expression was associated with disease-free survival (P = 0.0095) and was shown to be an independent risk factor for recurrence by multivariate analysis. In addition, we carried out an invasion assay in vitro to investigate whether cyclooxygenase-2 and matrix metalloproteinase-2 affected the tumor-invasive potential of colon cancer cell lines. The invasion assay showed that every cancer cell line acquired invasive potential in coculture with stromal cell lines and the cyclooxygenase-2 inhibitor suppressed this phenomenon by downregulating the matrix metalloproteinase-2 expression of stromal cells. In conclusion, these findings suggest that matrix metalloproteinase-2 expression in stromal cells can be a high-risk indicator for recurrence in patients with stage II colon cancer.

MeSH terms

  • Cell Line
  • Colonic Neoplasms / enzymology*
  • Colonic Neoplasms / pathology*
  • Cyclooxygenase 2 / metabolism
  • Cyclooxygenase 2 Inhibitors / pharmacology
  • Female
  • Gastrointestinal Stromal Tumors / enzymology*
  • Gastrointestinal Stromal Tumors / pathology*
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Male
  • Matrix Metalloproteinase 2 / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness / pathology
  • Neoplasm Staging
  • Prognosis
  • Survival Rate


  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase 2
  • Matrix Metalloproteinase 2