title: Sequential activation and production of matrix metalloproteinase-2 during breast cancer progression.
abstract: 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 +/- 7.2 mm2 in normal breasts, 7.7 +/- 9.8 mm2 in benign breast diseases, 9.5 +/- 8.5 mm2 in ductal carcinoma in situ (DCIS), and 12.0 +/- 13.7 mm2 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 diseases, 0.61 +/- 0.22 in DCIS, and 0.50 +/- 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.
authors.affiliation: Yonsei Cancer Center, Department of General Surgery, Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: K S
authors.initials: KS
authors.lastname: Lee
authors.forename: S Y
authors.initials: SY
authors.lastname: Rha
authors.forename: S J
authors.initials: SJ
authors.lastname: Kim
authors.forename: J H
authors.initials: JH
authors.lastname: Kim
authors.forename: J K
authors.initials: JK
authors.lastname: Roh
authors.forename: B S
authors.initials: BS
authors.lastname: Kim
authors.forename: H C
authors.initials: HC
authors.lastname: Chung
mesh_terms: D001940:Breast / Q000201:enzymology*; D001941:Breast Diseases / Q000201:enzymology; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000201:enzymology; D018450:Disease Progression; D004789:Enzyme Activation; D005260:Female; D018093:Gelatinases / Q000378:metabolism*; D006801:Humans; D020778:Matrix Metalloproteinase 2; D008666:Metalloendopeptidases / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D011379:Prognosis
chemical_list: D009363:Neoplasm Proteins; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2