AUGMENTATION OF TUMOR-METASTASIS BY PLATELET-ACTIVATING-FACTOR

The effect of platelet-activating factor (PAF) on experimental pulmona ry metastasis by the B16F10 murine melanoma and the possible involveme nt of PAF in the activities of tumor necrosis factor alpha (TNF-alpha) and interleukin 1 alpha (IL-1 alpha) in tumor metastasis were investi gated, 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 inje ctions of PAF mere more effective than a single injection, Neutralizat ion of endogenous PAF with PAF antagonist BN50739 decreased lung colon ization, suggesting that endogenous PAF plays an important role in pul monary metastases, A single i,p. injection of TNF-alpha or IL-1 alpha caused a marked enhancement in lung colonization. TNF-alpha- and IL-1 alpha-mediated enhancement in lung colonies was significantly inhibite d by BN50739, These results demonstrate that PAF has a metastasis-enha ncing effect and is a mediator of the metastatic activities of TNF-alp ha and IL-1 alpha.