Inhibition of
tumor angiogenesis represents a promising new approach for the treatment of human
cancers. It has remained unclear, however, whether inhibition of
tumor angiogenesis may also result in impaired wound healing, a process thought to be angiogenesis dependent. To determine the effects of the
angiogenesis inhibitor vasostatin, a 180
amino acid calreticulin fragment, on wound healing at
tumor inhibiting doses, full-thickness
wounds were generated on the back of nude mice that were also injected intradermally with CA46
Burkitt lymphoma cells. Mice were treated with daily
injections of
vasostatin or vehicle control at a site between the
wounds and the transplanted
tumor cells over 14 d.
Vasostatin potently inhibited
tumor growth and significantly reduced
tumor angiogenesis, as measured by computer-assisted image analysis of CD31-stained
tumor sections. Moreover,
vasostatin treatment resulted in an increased fraction of mature
tumor-associated blood vessels. In contrast, no impairment of wound healing was observed in
vasostatin-treated mice, despite a significantly reduced vascularity of the
wound granulation tissue. Our results reveal a different sensitivity of malignant
tumor growth and physiologic wound healing to inhibition of angiogenesis, and they suggest that therapeutic inhibition of
tumor angiogenesis may be achieved without impairment of tissue repair.