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See detailContribution of Host MMP-2 and MMP-9 to Promote Tumor Vascularization and Invasion of Malignant Keratinocytes
Masson, Véronique ULg; de la Ballina, L. R.; Munaut, Carine ULg et al

in FASEB Journal (2005), 19(2), 234-6

The matrix metalloproteinases (MMPs) play a key role in normal and pathological angiogenesis by mediating extracellular matrix degradation and/or controlling the biological activity of growth factors ... [more ▼]

The matrix metalloproteinases (MMPs) play a key role in normal and pathological angiogenesis by mediating extracellular matrix degradation and/or controlling the biological activity of growth factors, chemokines, and/or cytokines. Specific functions of individual MMPs as anti- or proangiogenic mediators remain to be elucidated. In the present study, we assessed the impact of single or combined MMP deficiencies in in vivo and in vitro models of angiogenesis (malignant keratinocyte transplantation and the aortic ring assay, respectively). MMP-9 was predominantly expressed by neutrophils in tumor transplants, whereas MMP-2 and MMP-3 were stromal. Neither the single deficiency of MMP-2, MMP-3, or MMP-9, nor the combined absence of MMP-9 and MMP-3 did impair tumor invasion and vascularization in vivo. However, there was a striking cooperative effect in double MMP-2:MMP-9-deficient mice as demonstrated by the absence of tumor vascularization and invasion. In contrast, the combined lack of MMP-2 and MMP-9 did not impair the in vitro capillary outgrowth from aortic rings. These results point to the importance of a cross talk between several host cells for the in vivo tumor promoting and angiogenic effects of MMP-2 and MMP-9. Our data demonstrate for the first time in an experimental model that MMP-2 and MMP-9 cooperate in promoting the in vivo invasive and angiogenic phenotype of malignant keratinocytes. [less ▲]

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See detailResistance of collagenase-2 (MMP-8) deficient mice to TNF-induced lethal hepatitis
Van Lint, Ph; Wielockx, B.; Puimege, L. et al

in Journal of Immunology (2005), 175(11), 7642-9

Acute fulminant liver failure is a serious worldwide health problem. Despite maximal supportive intensive care treatment, the disease offers a poor prognosis, with mortality rates of >80%. We have ... [more ▼]

Acute fulminant liver failure is a serious worldwide health problem. Despite maximal supportive intensive care treatment, the disease offers a poor prognosis, with mortality rates of >80%. We have previously shown that a broad-spectrum inhibitor of matrix metalloproteinases (MMPs) confers complete protection in a mouse model of TNF-induced lethal hepatitis, thereby suggesting the possibility of protecting cancer patients against the deleterious side effects of TNF therapy. In our search for the individual matrix metalloproteinases involved, we found that the recently generated MMP-8-deficient mice are significantly protected against TNF-induced acute hepatitis. In contrast to their wild-type counterparts, MMP-8-null mice display very little hepatocyte necrosis and apoptosis, resulting in a much better survival outcome. We found that these animals clearly display impaired leukocyte influx into the liver and no release of the neutrophil-specific, LPS-induced CXC chemokine. Our findings provide evidence that MMP-8 plays an essential role in acute liver failure and might be a promising new target for the treatment for this illness. [less ▲]

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