Growth inhibition of human papillary thyroid carcinoma cells and multicellular spheroids by anti-EGF-receptor antibody

EGF has been reported to stimulate thyroid cell proliferation. In the present study we investigated the effects of anti-EGF-R-antibody (Mab 4253 both as monolayers and spheroids of an oxyphilic, non iodine metabolizing, papillary thyroid carcinoma cell line (ONCO-DG-I) and roughly characterized their EGF-R. Scatchard analysis with 1-125-labeled-EGF demonstrated a low number of 1.5 x 10 4 EGF-R per monolayer cell (KD 4.1 x 10 -10 M) and only 6 x 10 3 EGF-R per spheroids cell (KD 5.0 x 10 -10 M). Already 80% of the binding sites were blocked by only 0.44 μg/ml Mab 425. Proliferathe activity and EGF-R were found to be regularly distributed throughout the spherolds. Adding Mab 425 to medium containing 1 ng/ml EGF, inhibited the growth of monolayer cells by 15% (1 ng/ml Mab 425) and 28% (10 ngiml Mab 425), measured by the MTT-test. The volume growth of spheroids was inhibited by 10-15% using 2 μg/ml Mab 425, whereas their viabilty (MTT-Test) was almost identical. The results show that the anti-EGF-R-antibody (Mab 425) alone is not effective enough for therapeutical use, but it could be of clinical value in conjugation with radionuclides (e.g. I-131) in order to reach metastases not metabolizing iodine.