Researchers from the University of California, San Diego, USA investigated the effect of heparin treatment on tumor metastasis.
They also assessed the relationship between heparin and the formation of tumor cell complexes with blood platelets.
The team found that heparin therapy attenuated tumor metastasis by inhibiting P-selectin-mediated interactions of platelets with carcinoma cell-surface mucin ligands.
Two human colon adenocarcinoma cell lines were used in the study.
|Heparin inhibits the P-selectin-mediated interaction of platelets with tumor cells.
|Proceedings of the National Academy of Sciences
In mice, selective removal of tumor mucin P-selectin ligands, a single heparin dose, or a background of P-selectin deficiency each reduced tumor cell-platelet interactions in vitro and in vivo.
Although each of these maneuvers reduced the in vivo interactions for only a few hours, all markedly reduced long-term organ colonization by tumor cells.
Three-dimensional reconstruction by using volume-rendering software showed that each situation interfered with formation of the platelet ‘cloak' around tumor cells while permitting an increase in the interaction of monocytes (macrophage precursors) with the malignant cells.
In addition, the researchers demonstrated that human P-selectin was even more sensitive to heparin than mouse P-selectin, giving significant inhibition at concentrations that were in the clinically acceptable range.
Dr Lubor Borsig, of the Glycobiology Research and Training Center, concluded on behalf of the group, "We suggest that heparin therapy for metastasis prevention in humans be revisited, with these mechanistic paradigms in mind."