Selective inhibition of matrix metalloproteinase-14 blocks tumor growth, invasion, and angiogenesis.

@article{Devy2009SelectiveIO,
  title={Selective inhibition of matrix metalloproteinase-14 blocks tumor growth, invasion, and angiogenesis.},
  author={Laetitia Devy and Lili Huang and Laurent Naa and Niranjan Yanamandra and Henk Pieters and Nicolas Frans and Edward F. Chang and Qi Tao and Marc Vanhove and Annabelle Lejeune and Reinoud van Gool and Daniel J. Sexton and Guannan Kuang and Douglas Rank and Shannon Hogan and Csaba Pazmany and Yu Lu Ma and Sonia Schoonbroodt and Andrew E. Nixon and Robert Charles Ladner and René M. A. Hoet and Paula Henderikx and Christopher Tenhoor and Shafaat A. Rabbani and M. L. Valentino and Clive Ross Wood and Daniel T. Dransfield},
  journal={Cancer research},
  year={2009},
  volume={69 4},
  pages={
          1517-26
        }
}
Inhibition of specific matrix metalloproteinases (MMP) is an attractive noncytotoxic approach to cancer therapy. MMP-14, a membrane-bound zinc endopeptidase, has been proposed to play a central role in tumor growth, invasion, and neovascularization. Besides cleaving matrix proteins, MMP-14 activates proMMP-2 leading to an amplification of pericellular proteolytic activity. To examine the contribution of MMP-14 to tumor growth and angiogenesis, we used DX-2400, a highly selective fully human MMP… 
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References

SHOWING 1-10 OF 40 REFERENCES

Membrane type-1 matrix metalloproteinase and TIMP-2 in tumor angiogenesis.

Hydroxamate-type matrix metalloproteinase inhibitor batimastat promotes liver metastasis.

Because of batimastat treatment, human breast carcinoma cells metastasized to the liver in nude mice and that an increase of liver metastases of murine T-cell lymphoma cells was observed in syngeneic mice.

Anti-Invasive, Antitumoral, and Antiangiogenic Efficacy of a Pyrimidine-2,4,6-trione Derivative, an Orally Active and Selective Matrix Metalloproteinases Inhibitor

Ro-28-2653, a selective and orally bioavailable MMPI with inhibitory activity against MMPs expressed by tumor and/or stromal cells, is a potent antitumor and antiangiogenic agent.

Preclinical and Clinical Studies of MMP Inhibitors in Cancer

Comparing the ability of broad‐spectrum and various types of selective matrix metalloproteinase inhibitors to induce tendinitis and to exhibit anticancer effects in an animal cancer model shows that under conditions in which both systemic exposure and inhibitor potency are controlled, selective inhibitors are less pro‐tendinitic, but are weaker anticancer agents than broad-spectrum agents such as marimastat.

Matrix Metalloproteinase Inhibitors and Cancer—Trials and Tribulations

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.

Combined treatment with serine protease inhibitor aprotinin and matrix metalloproteinase inhibitor Batimastat (BB-94) does not prevent invasion of human esophageal and ovarian carcinoma cells in vivo.

The findings demonstrate that the inhibition pattern of cellular proteolytic activity achieved in vitro by a serine protease and an MMP inhibitor may lead to predictions that are not necessarily verified in vivo and may even have adverse effects.

Induction of membrane-type-1 matrix metalloproteinase by epidermal growth factor-mediated signaling in gliomas.

The results indicate that one mechanism of EGFR-mediated invasiveness in gliomas may involve the induction of MT1-MMP, and compounds additionally inhibited EGF-stimulated invasion in Matrigel Transwell assays.

Expression of membrane-type matrix metalloproteinase 1 (MT1-MMP) in tumor cells enhances pulmonary metastasis in an experimental metastasis assay.

Immunostaining of the consecutive tissue sections revealed that lung nodules expressing MT1-MMP were positive for gelatinase A as well, whereas MT1,MMP-negative cells were not stained for collagenase A at all, indicating that MT1 -MMP -expressing cells acquire specific ability to bind exogenous progelatinase A.

MT1-MMP Controls Tumor-induced Angiogenesis through the Release of Semaphorin 4D*

The results suggest that the proteolytic cleavage of Semaphorin 4D may provide a novel molecular mechanism by which membrane type 1-matrix metalloproteinase controls tumor-induced angiogenesis.

Type IV collagen induces matrix metalloproteinase 2 activation in HT1080 fibrosarcoma cells.

It is shown here that type IV collagen, a major component of basement membranes, promotes MMP-2 activation by HT1080 cells, consistent with the previous report that TIMP-2 degradation is probably linked to the MT1-MMP-dependent MMP -2 activation mechanism.