Transferrin dependence of Ga (NO3)3 inhibition of growth in human-derived small cell lung cancer cells

J Cell Biochem Suppl. 1996;24:276-87. doi: 10.1002/jcb.240630523.

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.

MeSH terms

  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology
  • Carcinoma, Small Cell / metabolism
  • Carcinoma, Small Cell / pathology*
  • Cell Division / drug effects
  • Culture Media / pharmacology
  • Gallium / pharmacology*
  • Growth Inhibitors / pharmacology*
  • Humans
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Neoplasm Proteins / antagonists & inhibitors*
  • Neoplasm Proteins / immunology
  • Receptors, Transferrin / antagonists & inhibitors*
  • Receptors, Transferrin / immunology
  • Transferrin / physiology*
  • Tumor Cells, Cultured / drug effects

Substances

  • Antibodies, Monoclonal
  • Culture Media
  • Growth Inhibitors
  • Neoplasm Proteins
  • Receptors, Transferrin
  • Transferrin
  • Gallium
  • gallium nitrate