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...

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