SEQUENTIAL ACTIVATION AND PRODUCTION OF MATRIX METALLOPROTEINASE-2 DURING BREAST-CANCER PROGRESSION

The proteolytic processes are thought to be the critical point in tumo r 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. In active MMP-2 (72 kD) was expressed in 53.6% of the normal and 66.6% of the canter tissues, respectively (P=0.77), while active MMP-2 (62 kD) was expressed in 28.6% and 73.0%, respectively (P=0.003). The enzymat ic activity of active MMP-2 (62 kD) measured in the gel band area was 4.0+/-7.2 mm(2) in normal breasts, 7.7+/-9.8 mm(2) in benign breast di seases, 9.5+/-8.5 mm(2) in ductal carcinoma in situ (DCIS), and 12.0+/ -13.7 mm(2) in invasive cancers. The MMP-2 activation ratio (62 kD/62 kD+72 kD) was 0.12+/-0.18 in normal tissues, 0.10+/-0.20 in benign dis eases, 0.61+/-0.22 in DCIS, and 0.50+/-0.28 in invasive cancers. In co nclusion, MMP-2 activation was the main cause of the increased 62 kD M MP-2 activity during the early phase of breast cancer, while productio n of MMP-2 supplemented the increased 62 kD affinity 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.