Abstract
The tissue microenvironment impacts health and disease by providing a dynamic media where cells interact with the extracellular matrix scaffold, and a sink for critical ligands that dictate cell function. These dynamics become altered in cancer development through dysregulated proteolysis that is in part controlled by tissue inhibitors of metalloproteinases (TIMPs). This chapter reviews TIMP evolution and structure, the metalloproteinase targets, and the substrate complexity arising from metalloproteinase function. Individually, TIMPs inhibit proteolysis in a temporally and spatially distinct manner, resulting in a variety of phenotypes arising from specific TIMP deficiencies. It also discusses the consequences of altered TIMP gene expression on cell proliferation, apoptosis, angiogenesis, invasion, and metastasis in cell culture systems and mouse models. Although TIMPs inhibit angiogenesis, invasion, and metastasis, their effects on cell proliferation and apoptosis are tissue specific and context dependent. These studies highlight the importance of TIMPs as cancer modifier genes.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2008 Springer Science + Business Media, LLC
About this chapter
Cite this chapter
Murthy, A., Cruz-Munoz, W., Khokha, R. (2008). TIMPs: Extracellular Modifiers in Cancer Development. In: Edwards, D., Høyer-Hansen, G., Blasi, F., Sloane, B.F. (eds) The Cancer Degradome. Springer, New York, NY. https://doi.org/10.1007/978-0-387-69057-5_20
Download citation
DOI: https://doi.org/10.1007/978-0-387-69057-5_20
Publisher Name: Springer, New York, NY
Print ISBN: 978-0-387-69056-8
Online ISBN: 978-0-387-69057-5
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)