Augmentation of Tumor Metastasis by Platelet-activating Factor

The effect of platelet-activating factor (PAF) on experimental pulmonary metastasis by the B16F10 murine melanoma and the possible involvement of PAF in the activities of tumor necrosis factor α (TNF-α) and interleukin 1α (IL-1α) in tumor metastasis were investigated. i.p. injection of PAF enhanced the lung colonization in a dose- and time-dependent manner. PAF enhanced lung colonization when it was administered after, but not before, B16F10 inoculation. Multiple injections of PAF were more effective than a single injection. Neutralization of endogenous PAF with PAF antagonist BN50739 decreased lung colonization, suggesting that endogenous PAF plays an important role in pulmonary metastases. A single i.p. injection of TNF-α or IL-1α caused a marked enhancement in lung colonization. TNF-α- and IL-1α-mediated enhancement in lung colonies was significantly inhibited by BN50739. These results demonstrate that PAF has a metastasis-enhancing effect and is a mediator of the metastatic activities of TNF-α and IL-1α.