Cancer and Trousseau syndrome: the missing link revealed
Ajit Varki and colleagues from the University of California, San Diego, have revealed why individuals presenting with Trousseau syndrome also mysteriously suffer from mucin-producing carcinomas and why the anti-clotting agent heparin, but not other antithrombotic agents, is capable of ameliorating Trousseau syndrome.
Trousseau syndrome involves the formation of platelet-rich aggregates (microthrombi) in small blood vessels, in individuals with mucin-rich adenocarcinomas. However, no molecular link between carcinoma mucins and thrombosis previously existed. Adenocarcinomas secrete abnormally glycosylated mucins into the bloodstream that present pathological binding sites for P- and L-selectins.
Hypothesizing that selectin interactions with circulating mucins might trigger the syndrome, Varki and colleagues injected purified carcinoma mucin preparations into mice, rapidly inducing platelet-rich microthrombi. These were diminished in P- and L-selectindeficient mice and by the anticoagulant heparin. Inhibition of endogenous thrombin did not block platelet aggregation. The authors therefore deduced that Trousseau syndrome is likely triggered by interactions of circulating carcinoma mucins with leukocyte L-selectin and platelet P-selectin without requiring accompanying thrombin generation. The authors also suggest that heparin was likely working by directly inhibiting P- and L-selectin interactions. This may also explain why Trousseau syndrome is ameliorated by heparin but not by other antithrombotic agents.
TITLE: Selectin-mucin interactions as a probable molecular explanation for the association of Trousseau syndrome with mucinous adenocarcinomas