Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Our previous study showed that proMMP-9 was activated by MMP-3 directly, and that proMMP-3 was activated by plasmin. It was postulated that the proMMP-9 activation mechanism through the protease-protease cascade existed even in vivo. The purpose of the present study was to clarify the clinical significance of the combined expression of MMP-9, MMP-3, and urokinase-type plasminogen activator (uPA) in colorectal cancer, and the role of MMP-3 or uPA expression as an activator for MMP-9. The expression of both MMP-9 and uPA was found to be correlated with liver metastasis, and with survival rate. The coexpression of MMP-9 and uPA by tumor cells was also significantly correlated with postoperative hepatic recurrence and survival rate. MMP-9 tended to be coexpressed with uPA, and was consistently associated with MMP-3 localized at the tumor-invasive front with inflammatory cells such as monocyte-macrophages. In gelatin zymography, the MMP-9 active form tended to be identified in the tumors that coexpressed both MMP-9 and uPA. We concluded that coexpression of MMP-9 and uPA in tumor tissues might be a useful predictive factor for postoperative survival and hepatic metastasis. The following activation mechanism for proteinase might occur: uPA coexpressed with MMP-9 activated plasminogen, and plasmin activated proMMP-3, which was secreted depending upon inflammatory infiltration, and then MMP-3 activated proMMP-9, resulting in colorectal cancer progression and metastasis.

Original publication




Journal article


J surg res

Publication Date





211 - 218


Carcinoma, Colorectal Neoplasms, Female, Humans, Male, Matrix Metalloproteinase 3, Matrix Metalloproteinase 9, Neoplasm Invasiveness, Neoplasm Recurrence, Local, Survival Analysis, Urokinase-Type Plasminogen Activator