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Human Lactoferrin Inhibits Growth of Solid Tumors and Development of Experimental Metastases in Mice¹

New York University, Department of Biology, New York, New York 10003

The antitumor effects of the multifunctional iron-binding glycoprotein, lactoferrin (Lf), were investigated. Lf inhibited growth in mice of transplantable solid tumors induced by v-ras transformed fibroblasts and a methylcholanthrene-induced fibrosarcoma. Lf also substantially reduced lung colonization (experimental metastasis) by B16-F10 melanoma cells in syngeneic mice. Iron-saturated and apo-Lf exhibited comparable levels of tumor inhibition and antimetastatic activity. Transferrin, a related iron-binding protein, had no effect on lung colonization. In the B16-F10 system, elimination of natural killer cell activity by pretreatment of mice with anti-asialo G_M1 antibody abrogated the effects of Lf, whereas inhibition of macrophage function with silica did not. The results demonstrate a novel activity for Lf and suggest a potentially important role for this molecule in the primary defense against tumorigenesis.

¹ Supported by NIH Grant GM-49515.

² To whom requests for reprints should be addressed, at Department of Biology, New York University, 1009 Main Building, 100 Washington Square East, New York, NY 10003.

Received 1/27/94. Accepted 3/18/94.

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