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. Copyright 2004 Taylor & Francis
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. Copyright 2004 Taylor & Francis
Authors: Nancy Gordon; Nadezhda V Koshkina; Shu-Fang Jia; Chand Khanna; Arnulfo Mendoza; Laura L Worth; Eugenie S Kleinerman Journal: Clin Cancer Res Date: 2007-08-01 Impact factor: 12.531
Authors: Christiane Gebhard; Andrea Fuchs-Baumgartinger; Ebrahim Razzazi-Fazeli; Ingrid Miller; Ingrid Walter Journal: Can J Vet Res Date: 2016-01 Impact factor: 1.310
Authors: A Reza Radjabi; Kenjiro Sawada; Sujatha Jagadeeswaran; Alfred Eichbichler; Hilary A Kenny; Anthony Montag; Katharina Bruno; Ernst Lengyel Journal: J Biol Chem Date: 2007-11-29 Impact factor: 5.157
Authors: Eric R Wagner; Gaurav Luther; Gaohui Zhu; Qing Luo; Qiong Shi; Stephanie H Kim; Jian-Li Gao; Enyi Huang; Yanhong Gao; Ke Yang; Linyuan Wang; Chad Teven; Xiaoji Luo; Xing Liu; Mi Li; Ning Hu; Yuxi Su; Yang Bi; Bai-Cheng He; Ni Tang; Jinyong Luo; Liang Chen; Guowei Zuo; Richard Rames; Rex C Haydon; Hue H Luu; Tong-Chuan He Journal: Sarcoma Date: 2011-02-22