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A cryptic collagen epitope (green) is exposed on some tumor blood vessels.

Inject monoclonal antibodies into an animal with a tumor, the treatment inhibits angiogenesis, and tumor growth stops. Sound familiar?

This time, however, there is a twist: the antibodies described by Xu et al. (page 1069) target a cryptic epitope in the extracellular matrix rather than a cellular growth factor, and the results suggest an important activity for collagen type IV in directing the growth of new blood vessels.

Recent work has shown that proteolytic enzymes like the matrix metalloproteinases are required for normal angiogenesis, but the significance of these findings remained unclear. In the new work, the authors analyzed a monoclonal antibody that binds to proteolyzed collagen-IV, but not to the intact triple helical form of the protein. The cryptic epitope, HUIV26, is not seen in the basement membranes of normal blood vessels, but becomes exposed in angiogenic and tumor-associated blood vessels. HUIV26 epitope exposure correlates with a loss of 1ß1 integrin binding and a gain of vß3 binding, and the monoclonal antibody can strongly inhibit angiogenesis and tumor growth in several animal models.

The collagen epitope (green) is associated with matrix metalloproteinase-2 (red).

The new results suggest that proteolysis of the extracellular matrix exposes cryptic sites, which then transduce signals required for angiogenesis. The authors are now searching for additional cryptic signaling sites in other extracellular matrix proteins, and have already found additional monoclonal antibodies that inhibit angiogenesis and tumor growth. They have also discovered that the HUIV26 epitope may be able to regulate other types of behavior in neuronal, epithelial, and tumor cells.

Alan W. Dove

alanwdove{at}earthlink.net

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Related Article

Proteolytic exposure of a cryptic site within collagen type IV is required for angiogenesis and tumor growth in vivo

Jingsong Xu, Dorothy Rodriguez, Eric Petitclerc, Jenny J. Kim, Masanori Hangai, S. Moon Yuen, George E. Davis, and Peter C. Brooks
J. Cell Biol. 2001 154: 1069-1080. [Abstract] [Full Text] [PDF]

This Article PDF (Full Text) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Dove, A. W. Search for Related Content PubMed Articles by Dove, A. W. Related Collections Related Article Social Bookmarking                      What's this?