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- Title
Neutralizing vascular endothelial growth factor activity inhibits thyroid cancer growth in vivo.
- Authors
Soh, E. Y.; Kim, K. J.; Eigelberger, M. S.; Wong, M. G.; Duh, Q. -Y.; Clark, O. H.
- Abstract
Background: Without angiogenesis, tumours cannot grow larger than a few millimetres in size, the limit of diffusion. Vascular endothelial growth factor (VEGF) is an endothelial-specific mitogen and is a major regulator of physiological and pathological angiogenesis. Higher levels of VEGF messenger RNA expression and VEGF production and secretion have been found in FTC-133 cells than normal thyroid cells. Methods: To investigate the relationship between VEGF and thyroid tumour angiogenesis and growth, human dermal matrix inoculated with FTC-133 cells was xenografted into nude mice or directly injected subcutaneously. To block the function of VEGF, the neutralizing anti-VEGF monoclonal antibody A.4.6.1 (mAb A.4.6.1) was injected intraperitoneally 100 μg per 0·2 ml twice weekly. As control, an antibody of the same isotype (immunoglobulin G[sub 1]), directed against the gP120 protein (Ab 5B6), or phosphate-buffered saline (PBS) was used. To evaluate the dermal matrix as a model for angiogenesis studies, rhVEGF was inoculated into the dermal matrix pocket and xenografted into mice. Results: In vivo study using the dermal matrix showed that the number of blood vessel ingrowths paralleled the concentra- tion of rhVEGF and was highest at the concentration of 100 ng ml[sup -1]. Mice treated with the mAb A.4.6.1 developed fewer blood vessels (mean 7 per high-power field (HPF)) than control mice (18 per HPF in Ab 5B6 and 22 per HPF in PBS) (P < 0·01). The size of tumours between mAb A.4.6.1- and Ab 5B6- or PBS-treated groups showed a significant difference from the second week after the inoculation of FTC-133 cells. The tumours from mice treated with mAb A.4.6.1 were smaller (mean(s.d.) 0·09(0·02) g at 5 weeks) than tumours from mice treated with Ab 5B6 (5·38(1·15) g) or PBS (4·00(0·72) g) (P < 0·001, two-tailed unpaired t test). Conclusion: VEGF is produced by thyroid cancer cell line FTC-133 and stimulates angiogen...
- Subjects
VASCULAR endothelium; THYROID cancer; GROWTH
- Publication
British Journal of Surgery, 2000, Vol 87, Issue 9, p1256
- ISSN
0007-1323
- Publication type
Abstract
- DOI
10.1046/j.1365-2168.2000.01601-46.x