title: Transferrin dependence of Ga (NO3)3 inhibition of growth in human-derived small cell lung cancer cells.
abstract: The effect of a combination of anti-transferrin receptor (TFR) antibody, 42/6, and Ga(NO3)3 on cell growth was examined in small cell lung cancer (SCLC) cell lines: classic, NCI-H209, NCI-H345, NCI-H510; and variant, NCI-H82 and NCI-N417. The role of TFR and transferrin (TF) in Ga(NO3)3 cellular uptake was also tested. Exogenous TF did not enhance the cytotoxicity of Ga. At > 3 micrograms/mL, Ga(NO3)3 inhibited growth in all cell lines in TF-supplemented or deficient media. At < 3 micrograms/mL, Ga stimulated growth for all cells but this effect was eliminated by TF or 42/6. Classic SCLC lines required 3-4-fold less exogenous gallium than variant lines to reduce cell number by 50%. The mean Ga uptake (ng/10(6) cells) in H345 and H209 cell lines was 4-5-fold compared to H82 and N417 uptake (P < 0.001). 42/6 reduced exogenous TF-stimulated growth. Antibody plus Ga(NO3)3 caused a slight further cell number decline in all cell lines in TF-supplemented or deficient media. These results suggest that the addition of 42/6 antibody treatment would not increase the effectiveness of Ga(NO3)3 in patients. Both exogenous and endogenous TF and TFR play an important role in Ga uptake in these cells.
authors.affiliation: Nuclear Medicine Department, University of Connecticut Health Center, Farmington 06030, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Weiner
authors.forename: I
authors.initials: I
authors.lastname: Avis
authors.forename: R D
authors.initials: RD
authors.lastname: Neumann
authors.forename: J L
authors.initials: JL
authors.lastname: Mulshine
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D018288:Carcinoma, Small Cell / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D003470:Culture Media / Q000494:pharmacology; D005708:Gallium / Q000494:pharmacology*; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology; D011990:Receptors, Transferrin / Q000037:antagonists & inhibitors* / Q000276:immunology; D014168:Transferrin / Q000502:physiology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D003470:Culture Media; D006131:Growth Inhibitors; D009363:Neoplasm Proteins; D011990:Receptors, Transferrin; D014168:Transferrin; D005708:Gallium; C027235:gallium nitrate