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

Cristina Ferrari, Serena Benassi, Francesca Ponticelli, Gabriella Gamberi, Paola Ragazzini, Laura Pazzaglia, Alba Balladelli, Franco Bertoni, Piero Picci
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引用次数: 55

Abstract

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.

MMP-9及其组织抑制剂TIMP-1在人骨肉瘤中的作用:42例随访1-16年的发现
背景:基质金属蛋白酶(MMPs)降解细胞外基质的活性受前酶激活和MMP组织抑制剂(TIMPs)抑制的控制。患者和方法:为了评估恶性肿瘤进展中的蛋白水解级联失衡,我们在42例高级别骨肉瘤(OS)患者中分别评估了MMP-2、MMP-9及其抑制剂TIMP-2和TIMP-1的组织表达和血清水平。免疫组化法检测活检组织中MMP-2、MMP-9、TIMP-2和TIMP-1的表达,ELISA法检测血清中MMP-2和TIMP-1的表达。根据随访情况将患者分为连续无病组、随访中诊断为转移组和诊断为转移组。结果:免疫组织化学表明MMPs和TIMPs之间存在不平衡,其中MMP-9在肿瘤进展中的作用比MMP-2更明显。骨肉瘤患者血浆中TIMP-1抑制剂含量高于对照组。TIMP-1的高值在后来发生转移和/或局部复发的患者组以及诊断时已发生转移的患者组中尤为明显。解释:我们的研究结果证实了TIMP-1作为MMP抑制剂的保护作用,但也显示了其作为生长因子的活性,强调了其在OS中的多功能作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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