The angiogenesis inhibitor vasostatin does not impair wound healing at tumor-inhibiting doses

Inhibition of tumor angiogenesis represents a promising new approach for th e treatment of human cancers. It has remained unclear, however, whether inh ibition of tumor angiogenesis may also result in impaired wound healing, a process thought to be angiogenesis dependent. To determine the effects of t he angiogenesis inhibitor vasostatin, a 180 amino acid calreticulin fragmen t, on wound healing at tumor inhibiting doses, full-thickness wounds were g enerated on the back of nude mice that were also injected intradermally wit h CA46 Burkitt lymphoma cells. Mice were treated with daily injections of v asostatin or vehicle control at a site between the wounds and the transplan ted tumor cells over 14 d. Vasostatin potently inhibited tumor growth and s ignificantly reduced tumor angiogenesis, as measured by computer-assisted i mage analysis of CD31-stained tumor sections. Moreover, vasostatin treatmen t resulted in an increased fraction of mature tumor-associated blood vessel s. In contrast, no impairment of wound healing was observed in vasostatin-t reated mice, despite a significantly reduced vascularity of the wound granu lation tissue. Our results reveal a different sensitivity of malignant tumo r growth and physiologic wound healing to inhibition of angiogenesis, and t hey suggest that therapeutic inhibition of tumor angiogenesis may be achiev ed without impairment of tissue repair.