Studies on the mechanisms responsible for inhibition of experimental metastasis of B16-F10 murine melanoma by pentoxifylline

Pentoxifylline (PTX), a methylxanthine derivative widely used as a hemorheo logical agent in the treatment of peripheral vascular disease, was studied to unveil the mechanisms responsible for its inhibitory action on B16-F10 e xperimental metastasis. In vitro pretreatment of B16-F10 cells with noncyto toxic concentrations of PTX significantly inhibited their adhesion to recon stituted basement membrane Matrigel(R) and type IV collagen as well as the relative activity of secreted 92 kD metalloproteinase. However, PTX pretrea tment of B16-F10 cells did not affect their in vitro invasiveness. Heteroty pic organ adhesion assays carried out with B16-F10 cells and suspended orga n tissues demonstrated that pretreatment with noncytotoxic concentrations o f PTX of both, tumor cells or lung tissue, brought about a dose-dependent i nhibition of melanoma cell adhesion to lung. Immunohistochemical studies us ing antibodies against CD31 adhesion molecule (PECAM-1) revealed that B16-F 10 cells adhere to lung endothelial cells. Our results suggest that PTX may exert its inhibitory effect on tumor lodgment, and as a consequence of tha t on experimental metastases, through an inhibitory action on cell adhesion molecules.