Matrix metalloproteinases and the regulation of tissue remodelling
TLDR
Recent studies in mice and flies point to essential roles of MMPs as mediators of change and physical adaptation in tissues, whether developmentally regulated, environmentally induced or disease associated.Abstract:
Matrix metalloproteinases (MMPs) were discovered because of their role in amphibian metamorphosis, yet they have attracted more attention because of their roles in disease. Despite intensive scrutiny in vitro, in cell culture and in animal models, the normal physiological roles of these extracellular proteases have been elusive. Recent studies in mice and flies point to essential roles of MMPs as mediators of change and physical adaptation in tissues, whether developmentally regulated, environmentally induced or disease associated.read more
Citations
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Journal ArticleDOI
Matrix Metalloproteinases: Regulators of the Tumor Microenvironment
TL;DR: In addition to their role in extracellular matrix turnover and cancer cell migration, MMPs regulate signaling pathways that control cell growth, inflammation, or angiogenesis and may even work in a nonproteolytic manner.
Journal ArticleDOI
Matrix Crosslinking Forces Tumor Progression by Enhancing Integrin Signaling
Kandice R. Levental,Hongmei Yu,Laura Kass,Johnathon N. Lakins,Mikala Egeblad,Janine T. Erler,Sheri F. T. Fong,Katalin Csiszar,Amato J. Giaccia,Wolfgang Weninger,Mitsuo Yamauchi,David L. Gasser,Valerie M. Weaver +12 more
TL;DR: Reduction of lysyl oxidase-mediated collagen crosslinking prevented MMTV-Neu-induced fibrosis, decreased focal adhesions and PI3K activity, impeded malignancy, and lowered tumor incidence, and data show how collagenCrosslinking can modulate tissue fibrosis and stiffness to force focal adhesion, growth factor signaling and breast malignancies.
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The extracellular matrix: A dynamic niche in cancer progression
TL;DR: The extracellular matrix (ECM), a complex network of macromolecules with distinctive physical, biochemical, and biomechanical properties, is commonly deregulated and becomes disorganized in diseases such as cancer.
Journal ArticleDOI
A Tense Situation: Forcing Tumour Progression
TL;DR: The changing force that cells experience needs to be considered when trying to understand the complex nature of tumorigenesis.
Journal ArticleDOI
Extracellular Matrix Degradation and Remodeling in Development and Disease
TL;DR: Understanding the mechanisms of ECM remodeling and its regulation is essential for developing new therapeutic interventions for diseases and novel strategies for tissue engineering and regenerative medicine.
References
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Journal ArticleDOI
New functions for the matrix metalloproteinases in cancer progression
Mikala Egeblad,Zena Werb +1 more
TL;DR: It is shown that the MMPs have functions other than promotion of invasion, have substrates other than components of the extracellular matrix, and that they function before invasion in the development of cancer.
Journal ArticleDOI
How Matrix Metalloproteinases Regulate Cell Behavior
Mark D. Sternlicht,Zena Werb +1 more
TL;DR: Recent advances shed light on how the structure and function of the MMPs are related and on how their transcription, secretion, activation, inhibition, localization, and clearance are controlled.
Journal ArticleDOI
Matrix Metalloproteinases: A Review
Henning Birkedal-Hansen,William G. I. Moore,M.K. Bodden,L.J. Windsor,B. Birkedal-Hansen,Arthur A. Decarlo,Jeffrey A. Engler +6 more
TL;DR: The present review discusses in detail the primary structures and the overlapping yet distinct substrate specificities of MMPs as well as the mode of activation of the unique MMP precursors.
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Matrix Metalloproteinase Inhibitors and Cancer—Trials and Tribulations
TL;DR: The studies that brought MPIs into clinical testing are reviewed and the design and outcome of the trials are discussed in light of new information about the cellular source, substrates, and mode of action of MMPs at different stages of tumor progression.
Journal ArticleDOI
Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis
Gabriele Bergers,Rolf A. Brekken,Gerald McMahon,Thiennu H. Vu,Takeshi Itoh,Kazuhiko Tamaki,Kazuhiko Tanzawa,Philip E. Thorpe,Shigeyoshi Itohara,Zena Werb,Douglas Hanahan +10 more
TL;DR: The results show that MMP-9 is a component of theAngiogenic switch, and MMP inhibitors reduce angiogenic switching, and tumour number and growth, as does genetic ablation of M MP-9.
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