SEQUENTIAL PRODUCTION AND ACTIVATION OF MATRIX-METALLOPROTEINASE-9 (MMP-9) WITH BREAST-CANCER PROGRESSION

The degradation of the basement membrane by matrix-metalloproteinase ( MMP) and serine protease is a critical point in tumor invasion and met astasis. We measured the activity of MMP-9 from 28 normal, 12 benign a nd 126 breast cancer tissues using gelatin zymography with an image an alysis system. ProMMP-9 was expressed in 17.5% of the cancer patients compared to 2.5% in 40 non-cancerous tissues (p = 0.014). The mature f orm of MMP-9 (82 kD) was expressed only in T2-T4 stages. During the ea rly phase of breast cancer (DCIS and T1 stage) progression, only produ ction of proMMP-9 increased. However, as the cancer grew or invaded sk in (T2-T4), or with lymphovascular permeation, both production and act ivation of MMP-9 increased. In conclusion, proMMP-9 production was the main cause of increased MMP-9 activity during the early phase, while both production and activation increased in the late phase of breast c ancer.