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Complex roles of tissue inhibitors of metalloproteinases in cancer

Oncogene volume 21, pages 2245–2252 (2002)Cite this article

Abstract

Matrix metalloproteinases (MMPs) is tightly associated with extracellular matrix (ECM) turnover, which plays a very active role in tumor invasion and metastasis. Tissue inhibitors of metalloproteinases (TIMPs) plays a critical role in the homeostasis of ECM by regulating the activity of MMPs. TIMPs are well-known for their ability to inhibit MMP activity thereby inhibiting tumor growth and metastasis. However, many evidences suggest that TIMPs are multifunctional proteins, which regulate cell proliferation, apoptosis, proMMP-2 activation, and angiogenesis. These effects may be through MMP-dependent or MMP-independent pathways. Recent data indicate that TIMPs have many paradoxical roles in tumorigenesis. In particular, both inhibitory effect and stimulatory effect on tumorigenesis have been demonstrated in many animal models in which TIMPs were overexpressed in cancer cells or in mice. Elevated TIMP levels are reported in association with cancer progression and identified as poor prognostic indicators in several human tumor types. Herein, we review the complex roles of TIMPs in cancer growth and metastasis.

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Acknowledgements

This work was supported in part by grant CA68064-01 from National Institute of Health and grant DAMD17-96-1-6261 from US Department of Army Breast Cancer Research Program.

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  1. Department of Radiation Oncology, Long Island Jewish Medical Center, The Long Island Campus, Albert Einstein College of Medicine, New Hyde Park, New York, 11040, NY, USA

    Yangfu Jiang, Itzhak D Goldberg & Y Eric Shi

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Correspondence to Y Eric Shi.

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Jiang, Y., Goldberg, I. & Shi, Y. Complex roles of tissue inhibitors of metalloproteinases in cancer. Oncogene 21, 2245–2252 (2002). https://doi.org/10.1038/sj.onc.1205291

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