EPIDERMAL GROWTH-FACTOR ENHANCES PROLIFERATION, MIGRATION, AND INVASION OF FOLLICULAR AND PAPILLARY THYROID-CANCER IN-VITRO AND IN-VIVO

The prognosis of patients with follicular (FTC) and papillary (PTC) th yroid cancer depends on age and the size and extent of the tumor. Diff erentiated thyroid cancers bind more epidermal growth factor (EGF) tha n normal thyroid tissue, but the role of EGF in the proliferation and invasion of thyroid cancer is unknown. We investigated the effects of EGF on growth, migration, and invasion in a follicular thyroid cancer that metastasized to cervical lymph nodes and the lung (FTC 133, prima ry; FTC 236, lymph node; and FTC 238, lung metastasis) and in a papill ary thyroid cancer (PTC-UC3). As measured by the formazan method (dime thylthiazol-diphenyltetrazolium bromide), EGF caused a dose- and time- dependent increase in the growth of FTC 133 and PTC-UCB by 25%, but it s stimulatory effect on growth of the metastatic FTC subclones was sma ller (FTC 236, 14%; FTC 238, 8%; P < 0.001). EGF also enhanced the abi lity of all cell lines to migrate (through 8-mu m pore membranes witho ut Matrigel) or invade (mem branes with Matrigel). Migration of FTC 13 3 was enhanced from 86% migrated tumor cells to 95% after 72 h (P < 0. 02). Again, stimulation by EGF was lower in FTC 236 and FTC 238. EGF i ncreased migration in PTC-UC3 from 49% to 58%. EGF stimulated invasion of FTC 133 from 17.5% to 24.9%. In the absence of EGF, FTC 238 was th e most invasive tumor, but, again, the EGF stimulatory effect was less pronounced than in the primary tumor. EGF stimulated the invasion of PTC-UC3 from 10.9% to 14.3% (P < 0.03). EGF also stimulated the growth of thyroid cancer xenografts in nude mice. Although all FTC cell line s were 100% tumorigenic in nude mice, PTC-UC3 was less tumorigenic. Ho wever, after sc inoculation of EGF-pretreated tumor cells, 7 of 10 ani mals developed tumors (mean size, 2.3 cm(3)) compared to 2 of 10 anima ls (mean size, 1.4 cm(3)) in the control group (P < 0.02). In summary, EGF stimulates the growth and invasion of differentiated thyroid canc er cells in culture and in nude mice. Escape from growth factor contro l, such as in FTC 236 and FTC 238, may be an important step in the dev elopment of metastatic thyroid cancer.