Neutralizing vascular endothelial growth factor activity inhibits thyroid cancer growth in vivo

Background. Without angiogenesis, tumor growth is limited to a few millimet ers, the limit of diffusion. Vascular endothelial growth factor (VEGF) is a n endothelial-specific mitogen and a major regulator of angiogenesis. Methods. To investigate the relationship between VEGF and thyroid tumor ang iogenesis, we xenografted human dermal matrix inoculated with FTC-133 cells into nude mice or directly injected FTC-133 cells subcutaneously. To bloch the function of VEGF, the neutralizing anti-VEGF monoclonal antibody A.4.6 .1 (mAb A.4.6.1) was injected intraperitoneally twice weekly. As control, a n antibody of the same isotype (Ab 5B6) or phosphate buffer saline solution (PBS) was used. To evaluate the dermal matrix as a model for angiogenesis studies, recombinant human VEGF was inoculated into the dermal matrix pocke t and xenografted into mice. Results. In the dermal matrix angiogenesis model, the number of blood vesse ls paralleled the concentration of recombinant human VEGF and was highest a t 100 ng/mL, Mice that were treated with the mAb A4.6.1 developed fewer blo od vessel (mean, 6.6 per HPF) than control mice (18 per HPF in Ab 5B6 and 2 2 per HPF in PBS; P < .01). Tumors from mice that were treated with mAb A.4 .6.1 were much smaller (mean +/- SD, 0.09 +/- 0.02 gm) at 5 weeks, compared with the tumors treated with Ab 5B6 (5.38 +/- 1.15 gm) or PBS (4.0 +/- 0.7 2 gm; P < .001). Conclusions. VEGF is produced by the follicular thyroid cancer cell line an d stimulates angiogenesis and growth of thyroid cancer This stimulation can be blocked by mAb A.4.6.1.