Chemically modified heparin inhibits the in vitro adhesion of nonsmall cell lung cancer cells to P-selectin

Purpose: Several independent studies have indicated that tumor metastasis can be inhibited by chemically modified heparin with low anticoagulant activity in the different tumor models. The mechanism of inhibition by the heparin derivatives in part accounts for the interference of tumor cell-platelet interaction mediated by P-selectin. Methods: In the present study, we demonstrated that both heparin and chemically modified heparins inhibited the adhesion of nonsmall cell lung cancer (NSCLC) cells to P-selectin under static or flow conditions in vitro. Results: Flow cytometric analysis with the heparan sulfate-specific monoclonal antibody revealed that both NSCLC cells express heparan sulfate-like proteoglycans. Furthermore, heparinase treatment impaired P-selectin binding, indicating that heparan sulfate-like proteoglycans on the tumor cell surface are implicated in the adhesion of NSCLC cells to P-selectin. Conclusions: These findings suggest that some chemically modified heparins with low anticoagulant activity may deserve further testing in the experimental NSCLC treatment protocols.