Role of MMP-9 and its tissue inhibitor TIMP-1 in human osteosarcoma - Findings in 42 patients followed for 1-16 years

被引:39
作者
Ferrari, C [1 ]
Benassi, MS
Ponticelli, F
Gamberi, G
Ragazzini, P
Pazzaglia, L
Balladelli, A
Bertoni, F
Picci, P
机构
[1] Rizzoli Orthopaed Inst, Lab Oncol Res, Bologna, Italy
[2] Rizzoli Orthopaed Inst, Dept Pathol, Bologna, Italy
来源
ACTA ORTHOPAEDICA SCANDINAVICA | 2004年 / 75卷 / 04期
关键词
D O I
10.1080/00016470410001295-1
中图分类号
R826.8 [整形外科学]; R782.2 [口腔颌面部整形外科学]; R726.2 [小儿整形外科学]; R62 [整形外科学(修复外科学)];
学科分类号
摘要
Background The activity of matrix metalloproteinases (MMPs) in degrading extracellular matrix is controlled by activation of proenzymes and inhibition of MMP tissue inhibitors (TIMPs). Patients and methods To assess the proteolytic cascade imbalance in malignancy progression, tissue expression and serum levels of MMP-2, MMP-9 and of their inhibitors TIMP-2 and TIMP-1 respectively were evaluated in 42 selected patients with high-grade osteosarcoma (OS). MMP-2, MMP-9, TIMP-2 and TIMP-1 were studied in biopsies by immunohistochemistry and in serum by ELISA test. Patients were subdivided into 3 groups according to their follow up: continuously disease-free, diagnosis of metastasis during follow-up, and metastasis at diagnosis. Results Immunohistochemistry demonstrated an imbalance between MMPs and TIMPs, with a more evident role for MMP-9 than for MMP-2 in tumor progression. TIMP-1 inhibitor in plasma was higher in patients with osteosarcoma than in a control group. This high value of TIMP-1 was particularly evident in the group of patients who later developed metastases and/or local recurrences, and in those with metastases at diagnosis. Interpretation Our findings confirm the protective action of TIMP-1, as MMP inhibitor, but also show its activity as a growth factor underlining its multifunctional role in OS.
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页码:487 / 491
页数:5
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