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Stimulation of angiogenesis through cathepsin B inactivation of the tissue inhibitors of matrix metalloproteinases



Stimulation of angiogenesis through cathepsin B inactivation of the tissue inhibitors of matrix metalloproteinases



Febs Letters 455(3): 286-290



The tissue inhibitors of matrix metalloproteinases (MMPs), TIMP-1 and TIMP-2, are also angiogenesis inhibitors. Cathepsin B and MMPs are found at sites of neovascularization in pathologies such as cancer and osteoarthritis. Treatment of TIMP-1, TIMP-2, and of a mixture of both inhibitors from human articular chondrocytes with cathepsin B resulted in their fragmentation, whereby they lost their MMP-inhibitory and anti-angiogenic activities. Our data suggest that, besides directly participating in tissue destruction, cathepsin B can be harmful for two further reasons: it raises the activity of the MMPs also in the absence of mechanisms up-regulating these enzymes, and it stimulates angiogenesis. This is a prerequisite for blood vessel invasion in a variety of pathological situations of which cancer and osteoarthritis are prominent examples.

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Accession: 047441370

Download citation: RISBibTeXText

PMID: 10437790

DOI: 10.1016/s0014-5793(99)00897-2


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