The proteolytic processes are thought to be the critical point in tumor invasion and metastasis, mainly by matrix metalloproteinases (MMPs) and serine proteases. We measured the activity of MMP-2 from 28 normal, 12 benign and 126 breast cancer tissues using gelatin zymography. Inactive MMP-2 (72 kD) was expressed in 53.6% of the normal and 66.6% of the cancer tissues, respectively (P = 0.77), while active MMP-2 (62 kD) was expressed in 28.6% and 73.0%, respectively (P = 0.003). The enzymatic activity of active MMP-2 (62 kD) measured in the gel band area was 4.0 Β± 7.2 mm 2 in normal breasts, 7.7 Β± 9.8 mm 2 in benign breast diseases, 9.5 Β± 8.5 mm 2 in ductal carcinoma in situ (DCIS), and 12.0 Β± 13.7 mm 2 in invasive cancers.
The MMP-2 activation ratio (62 kD/62 kD + 72 kD) was 0.12 Β± 0.18 in normal tissues, 0.10 Β± 0.20 in benign diseases, 0.61 Β± 0.22 in DCIS, and 0.50 Β± 0.28 in invasive cancers. In conclusion, MMP-2 activation was the main cause of the increased 62 kD MMP-2 activity during the early phase of breast cancer, while production of MMP-2 supplemented the increased 62 kD activity in the late phase. We suggest, therefore, that these differential expressions of MMP-2 activation and production during the different stages of breast cancer progression are potential therapeutic targets for biological or gene therapy under the concept of stage-oriented cancer treatment.