Chemically Modified Heparin Inhibits In Vitro L-Selectin-Mediated Human Ovarian Carcinoma Cell Adhesion

Abstract

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.

The Anticoagulant and Nonanticoagulant Properties of Heparin

“…Likewise, the mentioned inhibitory interaction of heparins with selectins is independent of the anticoagulant function of heparin and was described also for chemically modified forms of heparin in vitro. 79 As the hemostatic system is involved in cancer development, it remains to be proven what the true therapeutic value of inclusion of nonanticoagulant heparin in cancer treatment is and what the best treatment strategy is in current clinical practice. Hence, the possibility that different types of heparin have different therapeutic effects in various types of cancer should be considered.…”

Antitumor Effect of Butanoylated Heparin with Low Anticoagulant Activity on Lung Cancer Growth in Mice and Rats

“…However, they did not show data on selectin and inhibi-tion of tumor growth. In addition, Chen and co-workers reported that chemically modified heparin derivate significantly inhibited L-selectin binding to human overian cancer cells [71]. Our work in this study was focused on antitumor growth, revealing that p53-Rb-E2F pathway was involved in this inhibition of lung cancer tumor growth.…”

Preparation and identification of a novel immunomodulator composed of muramyl dipeptide and anti-CD10 monoclonal antibody for treatment of minimal residual disease in acute leukemia children

“…At present, many methods are used to construct the new agents targeting cancer therapy, such as the Valeraldehyde method, the sodium periodate method [36,37], and nanoparticles. However, the isomers were produced and difficultly purified.…”