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-1) and roughly characterized their EGF-R. Scatchard analysis with I-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 microgram/ml Mab 425. Proliferathe activity and EGF-R were found to be regularly distributed throughout the spheroids. 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 micrograms/ml Mab 425, whereas their viability (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.
Gabler
B
B
Nuklearmedizinische Klinik, Technischen Universität München, Germany.
Aicher
T
T
Heiss
P
P
Senekowitsch-Schmidtke
R
R
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002291:Carcinoma, Papillary / Q000473:pathology / Q000628:therapy*; D066246:ErbB Receptors / Q000502:physiology*; D006801:Humans; D051379:Mice; D018874:Spheroids, Cellular; D013964:Thyroid Neoplasms / Q000473:pathology / Q000628:therapy*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D066246:ErbB Receptors