Association of cyclooxygenase-2 and matrix metalloproteinase-2 expression in human breast cancer
- 1 February 2005
- journal article
- other
- Published by Springer Nature in Breast Cancer Research and Treatment
- Vol. 89 (3) , 215-220
- https://doi.org/10.1007/s10549-004-0714-4
Abstract
Expression of cyclooxygenase-2 (COX-2) and matrix metalloproteinase-2 (MMP-2) associates with reduced survival in human breast cancer. COX-2 may be directly involved with mammary carcinogenesis, since expression of COX-2 is sufficient for formation of breast tumors in transgenic mice, and COX-2 selective inhibitors can suppress tumorigenesis in rodent models of breast cancer. MMP-2 is an extracellular matrix degrading proteolytic enzyme that bas been linked to invasion and metastasis. A direct link between COX-2 and MMP-2 may exist, since inhibition of COX-2 activity can result in reduction of MMP-2 expression and activity. In this study we analyzed protein expression of COX-2 and MMP-2 in tissue array specimens of 278 invasive breast cancers by immunohistochemistry. Immunopositivity of these two markers was correlated with each other and with various clinicopathological parameters including survival. We found high COX-2 expression in 30% and high MMP-2 expression in 83% of the breast cancer specimens, and there was a positive association between the expression of these two factors (p=0.003). It was especially evident that whenever COX-2 expression was high, MMP-2 expression was almost invariably high (95%). Furthermore, high expression of either COX-2 or MMP-2 associated with decreased disease specific survival when compared with the COX-2 or MPP-2 low group (p=0.026 and p=0.021, respectively). Taken together, our results indicate that expression of COX-2 protein is associated with expression of MMP-2 protein in human breast cancer and that both COX-2 and MMP-2 are markers of poor prognosis in breast cancer.Keywords
This publication has 20 references indexed in Scilit:
- Matrix metalloproteinase-2 (MMP-2) is associated with survival in breast carcinomaBritish Journal of Cancer, 2003
- Elevated expression of cyclooxygenase‐2 is a negative prognostic factor for disease free survival and overall survival in patients with breast carcinomaCancer, 2003
- Correlation of COX-2 and Ep-CAM overexpression in human invasive breast cancer and its impact on survivalBritish Journal of Cancer, 2003
- Autocrine/Paracrine Prostaglandin E2 Production by Non-small Cell Lung Cancer Cells Regulates Matrix Metalloproteinase-2 and CD44 in Cyclooxygenase-2-dependent InvasionJournal of Biological Chemistry, 2002
- Cyclo-oxygenase inhibition reduces tumour growth and metastasis in an orthotopic model of breast cancerBritish Journal of Cancer, 2002
- New functions for the matrix metalloproteinases in cancer progressionNature Reviews Cancer, 2002
- Chemoprevention by Nimesulide, a Selective Cyclooxygenase‐2 Inhibitor, of 2‐Amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP)‐induced Mammary Gland Carcinogenesis in RatsJapanese Journal of Cancer Research, 2000
- Tissue microarrays for high-throughput molecular profiling of tumor specimensNature Medicine, 1998
- Immunohistochemical localization of matrix metallloproteinase 2 and its specific inhibitor timp‐2 in neoplastic tissues with monclonal antibodiesInternational Journal of Cancer, 1994
- Metastatic potential correlates with enzymatic degradation of basement membrane collagenNature, 1980