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University of Colorado Health Sciences Center, Denver, Colorado 80262
In previous studies, we have demonstrated that transferrin-gallium inhibits cellular proliferation by a mechanism whereby cellular iron utilization is impaired. Since indium, a similar class 3A metal, has not been well studied, we examined its effects on cellular iron uptake and cellular proliferation. In these studies, we provide evidence that indium, when bound to transferrin, has a 50-fold higher effect on inhibition of cellular proliferation than indium added as indium salt. Cells exposed to relatively low concentrations of transferrin-indium exhibit markedly increased transferrin receptor expression but, as with transferrin-gallium, these cells incorporate an inappropriately low amount of iron, suggesting that there is a defect in the release of internalized iron from transferrin. In further studies, we utilize a monoclonal antibody against transferrin receptor that inhibits transferrin-mediated iron uptake. This antibody exhibits a dose-related inhibition of cellular proliferation, and when both transferrin-indium and monoclonal antibody are added to media, there is a more than additive effect on inhibition of cellular proliferation.
1 This work was supported by NIH/NHHS Grant AM 27039 (P. A. S.).
2 To whom requests for reprints should be addressed, at 4200 E. 9th Avenue, Box B-170, Denver, CO 80209.
Received 12/ 6/88. Revised 4/12/89. Accepted 4/28/89.
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