Chemically modified heparin inhibits in vitro L-selectin-mediated human ovarian carcinoma cell adhesion

Accumulating evidence indicates that hematogenous metastasis is facilitated by tumor cell-leukocyte emboli formation, and L-selectin plays a major role in the process. Several independent studies have indicated that tumor metastasis can be inhibited by chemically modified heparin with low anticoagulant activity in the different tumor models. In the present study, we demonstrated that chemically modified nonanticoagulation heparin derivate (periodate-oxidized, borohydride-reduced heparin [RO-heparin]) can inhibit the binding of L-selectin to HO-8910 cells, block the adhering of HO-8910 to Chinese hamster ovary cells expressing a transfected human L-selectin complementary DNA, and affect the interactions of neutrophils with HO-8910 cells. Flow cytometric analysis with the heparan sulfate-specific monoclonal antibody revealed that HO-8910 cells express heparan sulfate-like proteoglycans. Furthermore, heparinase treatment impaired L-selectin binding, indicating that heparan sulfate-like proteoglycans on the tumor cell surface are implicated in the binding of L-selectin to HO-8910 cells. These findings suggest that RO-heparin with low anticoagulant activities may have potential value as therapeutic agents that block L-selectin-mediated cell adhesion and prevent tumor metastasis.