Increased expression of collagenase-3 (MMP-13) and MT1-MMP in oesophageal cancer is related to cancer aggressiveness

Background-Collagenase-3 (matrix metalloproteinase-13, MMP-13) is a recentl y identified human MMP with broad substrate specificity which can be activa ted by membrane type 1 (MT1) matrix metalloproteinase in vitro. These may p lay a critical role in cancer aggressiveness. Aims-To examine the clinical significance of collagenase-3 expression and t he cooperative role of MT1-MMP in human oesophageal carcinomas. Patients-Forty five individuals with oesophageal carcinoma who underwent su rgery without preoperative treatment. Methods-The tumour/normal (T/N) ratios of collagenase-3 and MT1-MMP mRNA ex pression in 45 human oesophageal carcinomas were determined by northern blo t analysis. The production and localisation of collagenase-3 and MT1-MMP mR NA expression (p<0.001). Twenty two cases with a collagenase-3 T/N ratio >3 .5 showed a significantly higher frequency of vascular involvement and lymp h node metastasis, and tended to be at a more advanced stage than 23 cases with a T/N ratio less than or equal to 3.5 (p<0.05). Western blot analysis and zymography demonstrated production of collagenase-3 protein in tumour t issues but not in normal tissues. Immunohistochemical studies revealed that collagenase-3 was localised predominantly in tumour cells and MT1-MMP was detected in the same collagenase-3 positive cells; there was a significant association between collagenase-3 and MT1-MMP protein expression (p<0.05). With regard to prognosis, the survival time for subjects in the high collag enase-3 group (T/N ratio >3.5) was significantly worse (p<0.05). Conclusions-These data suggest that production of collagenase-3 together wi th MT1-MMP is implicated in tumour aggressiveness is implicated in tumour a ggressiveness and prognosis in human oesophageal carcinomas.