Matrix Metalloproteinases: Regulators of the Tumor Microenvironment

@article{Kessenbrock2010MatrixMR,
  title={Matrix Metalloproteinases: Regulators of the Tumor Microenvironment},
  author={Kai Kessenbrock and Vicki Plaks and Zena Werb},
  journal={Cell},
  year={2010},
  volume={141},
  pages={52-67}
}
Extracellular proteolysis mediates tissue homeostasis. In cancer, altered proteolysis leads to unregulated tumor growth, tissue remodeling, inflammation, tissue invasion, and metastasis. The matrix metalloproteinases (MMPs) represent the most prominent family of proteinases associated with tumorigenesis. Recent technological developments have markedly advanced our understanding of MMPs as modulators of the tumor microenvironment. In addition to their role in extracellular matrix turnover and… 
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References

SHOWING 1-10 OF 140 REFERENCES
Matrix metalloproteinases as modulators of inflammation.
TLDR
Developing rational therapies requires further identification of specific MMP substrates and characterization of the downstream consequences of MMP proteolytic activity.
Structure and function of matrix metalloproteinases and TIMPs.
TLDR
The members of the MMP family are introduced and their domain structure and function, proenyme activation, the mechanism of inhibition by TIMPs and their significance in physiology and pathology are discussed.
New functions for the matrix metalloproteinases in cancer progression
TLDR
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.
Matrix metalloproteinase-8 functions as a metastasis suppressor through modulation of tumor cell adhesion and invasion.
TLDR
It is proposed that MMP-8 is a tumor protective factor, which also has the ability to reduce the metastatic potential of malignant cells in both mice and human.
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.
The Stromal Proteinase MMP3/Stromelysin-1 Promotes Mammary Carcinogenesis
TLDR
P phenotypically normal mammary epithelial cells with tetracycline-regulated expression of MMP3/stromelysin-1 (Str1) form epithelial glandular structures in vivo without Str1 but form invasive mesenchymal-like tumors with Str1, indicating that Str1 influences tumor initiation and alters neoplastic risk.
Matrix metalloproteinases and tumor metastasis
TLDR
The major pieces of evidence that are most compelling and clearly determine the role and involvement of MMPs in the metastatic cascade are provided by molecular genetic studies employing knock-out or transgenic animals and tumor cell lines, modified to overexpress or downregulate a specific MMP.
Tumor cell traffic through the extracellular matrix is controlled by the membrane-anchored collagenase MT1-MMP
TLDR
It is found that fibroblasts and cancer cells express an indistinguishable pericellular collagenolytic activity that allows them to traverse the ECM and that MT1-MMP serves as the major cell-associated proteinase necessary to confer normal or neoplastic cells with invasive activity.
How matrix metalloproteinases regulate cell behavior.
TLDR
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.
Stromal regulation of vessel stability by MMP14 and TGFβ
TLDR
A central pathway involving MMP14 and TGFβ that mediates vessel stability and vascular response to tissue injury is defined and antagonists of this pathway could be therapeutically exploited to improve the delivery of therapeutics or molecular contrast agents into tissues where chronic damage or neoplastic disease limits their efficient delivery.
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2
3
4
5
...