TRANSFERRIN DEPENDENCE OF GA (NO3)(3) INHIBITION OF GROWTH IN HUMAN-DERIVED SMALL-CELL LUNG-CANCER CELLS

The effect of a combination of anti-transferrin receptor (TFR) antibod y, 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 enha nce the cytotoxicity of Ga. At > 3 mu g/mL, Ga(NO3)(3) inhibited growt h in all cell lines in TF-supplemented or deficient media. At < 3 mu g /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 ga llium than variant lines to reduce cell number by 50%. The mean Ga upt ake (ng/10(6) cells) in H345 and H209 cell lines tvas 4-5-fold compare d to H82 and N417 uptake (P < 0.001). 42/6 reduced exogenous TF-stimul ated growth. Antibody plus Ga(NO3)(3) caused a slight further cell num ber decline in all cell lines in TF-supplemented or deficient media. T hese results suggest that the addition of 42/6 antibody treatment woul d not increase the effectiveness of Ga(NO3)(3) in patients. Both exoge nous and endogenous TF and TFR play an important role in Ga uptake in these cells. (C) 1996 Wiley-Liss, Inc.