A STRATEGY TO DISCOVER CIRCULATING ANGIOGENESIS INHIBITORS GENERATED BY HUMAN TUMORS

The phenomenon of inhibition of tumor growth by tumor mass has been st udied in many experimental animal systems and has been observed in sev eral clinical scenarios. Not until the recent discovery of angiostatin , a circulating angiogenesis inhibitor generated in the presence of a murine Lewis lung tumor, has a satisfactory mechanism been proposed to explain this phenomenon. Thus far, no other animal or human tumors ar e known to generate angiostatin. In this study, we utilized a mouse co rneal neovascularization model to detect circulating inhibitors of ang iogenesis generated by three human tumors grown in immunodeficient mic e: (a) the PC-3 human prostate carcinoma; (b) the CCL188 human colon c arcinoma; and (c) the UBC urinary bladder carcinoma. Mice bearing thes e three primary tumors demonstrated significant inhibition of angiogen esis in the cornea induced by a pellet containing basic fibroblast gro wth factor. Corneas of mice bearing s.c. prostate and colon carcinomas showed significant inhibition of vessel length, clock-hours of neovas cularization, and vessel density. However, corneas of mice bearing s.c . bladder carcinomas demonstrated significant inhibition of vessel den sity only. Three colon carcinomas (clone A, CX-1, and MIP101), the MDA -MB-435S breast carcinoma, the MM-AN melanoma, and the JE-3 choriocarc inoma did not significantly inhibit corneal neovascularization.