These data do not provide any evidence that this inhibitor blocks tumor angiogenesis factor directly. Furthermore, there is no evidence that this inhibitor is specific to tumor-induced vessels. It remains to be seem whether systemic administration of the inhibitor will suppress tumor neovascularization in a manner similar to that demonstrated here by local delivery. One would like to try such an experiment in a rabbit or some other small animal, but at present not enough inhibitor from cartilage is available. The single factor most limiting to the further study of this substance is its supply.
Cartilage is present only in small quantities in mammalian species.
It occurred to us that sharks may be a potential source of this inhibitor because, unlike mammals, sharks have an endoskeleton composed entirely of cartilage. Sharks may contain as much as 100,000 times more angiogenesis inhibitory activity on a per animal basis. As in previous studies, Lee and Langer observed healthy tumor cells at the interface between the tumor and pellet containing the cartilage extract demonstrating that the inhibitory effect was on capillary growth and not directly against the tumor. It is not known whether all sharks contain angiogenesis inhibitors or whether the same molecule in calf and shark cartilage is responsible for the inhibition of tumor angiogenesis. Direct comparison of the two molecular characteristics of the two inhibitors must await their complete purification.