INVOLVEMENT OF MATRIX METALLOPROTEINASE-2 ACTIVITY IN INVASION AND METASTASIS OF PANCREATIC-CARCINOMA

BACKGROUND. Activation of matrix metalloproteinase-2 (MMP-2) has been implicated in the progression, invasion, and metastasis of various can cers, but little information is available with regard to its role in p ancreatic carcinoma with poor prognosis. METHODS. Gelatin zymography w as used for the detection of latent and activated forms of MMP-2 and M MP-9 in 13 normal pancreatic tissue specimens, 14 chronic pancreatitis tissue specimens, and 33 pancreatic carcinoma tissue specimens. The g elatinase activity was quantified by densitometer, and the 66-kilodalt on (kDa)/ (66-kDa + 72-kDa) ratio was calculated as the MMP-2 activati on ratio. Western blot analysis was performed to confirm the zymograph ic profile. RESULTS. Latent forms of MMP-2 and MMP-9 were detected in all samples of pancreatic carcinoma, chronic pancreatitis, and normal pancreatic tissue. The expression rate of the MMP-2 activated form in pancreatic carcinoma tissue specimens was 100% (33 of 33) but that of MMP-9 was 21%. The MMP-2 activation ratio in pancreatic carcinoma tiss ue specimens was significantly higher than that of chronic pancreatiti s and normal pancreatic tissue specimens. The MMP-2 activation ratio i n pT3 tumors was significantly higher than that in pT1 tumors. The MMP -2 activation ratio also was significantly higher in pancreatic carcin oma specimens with histologically positive regional lymph node metasta sis and distant metastasis than those without metastasis. The MMP-2 ac tivation ratio observed in patients who developed postresection recurr ence within 6 months was significantly higher than that in patients wi thout recurrence at 6 months. CONCLUSIONS. The results of the current study indicate that MMP-2 activation plays a significant role in tumor invasion and metastasis in pancreatic carcinoma. (C) 1998 American Ca ncer Society.