Chemically modified heparins inhibit fibrinogen-bridged indirect adhesion between tumor cells and platelets

Abstract

Abstract. The interaction between platelets and tumor cells is critical for the hematogenous metastasis of tumor cells. We recently reported that fibrinogen was capable of bridging and enhancing the interaction of platelets and tumor cells under conditions of physical shear force. In the present study, we aimed to detect the effects of 8 chemically modified heparins on the binding of fibrinogen to platelets or tumor cells using flow cytometry assays, as well as the fibrinogen-bridged adhesion of platelets and tumor cells using flow chamber assays. The results showed that fibrinogen binds to platelets and tumor cells in a β3 integrin-dependent manner and bridges the adhesion between platelets and tumor cells. Heparin and certain chemically modified heparins, including borohydride-reduced (RO)-, carboxyl-reduced (CR)-and 2-O, 3-O-desulfated (2/3ODS)-heparins, inhibited the β3 integrin-dependent adhesion of fibrinogen to platelets or tumor cells, and consequently blocked the fibrinogen-bridged indirect adhesion of platelets to tumor cells. These data indicate that chemically modified heparins should be potential inhibitors for the fibrinogen-bridged indirect adhesion of platelets and tumor cells, which provides a novel explanation of the anti-adhesion property of heparin and proposes a new anti-metastatic target for cancer treatment.

Platelet-derived extracellular vesicles inhibit ferroptosis and promote distant metastasis of nasopharyngeal carcinoma by upregulating ITGB3

“…Platelets are the major blood component involved in hemostasis and promote the distant metastasis of tumor cells via blood circulation 7 , 8 . However, the mechanism underlying platelet-tumor cell interaction remains unclear and is still an area of active investigation.…”

“…Platelets are anucleate blood cells generated from megakaryocytes that are required for hemostasis and thrombosis 7 . Recently, emerging evidence has established that platelets are versatile cells involved in the pathological processes of tumor cell hematogenous metastasis, a process in which tumor cells transit from the primary tumor to distant organs via blood circulation 7 , 8 . Platelets enhance the hematogenous metastasis of tumor cells, a complex process that helps tumor cells escape immunosurveillance and arrest, adhere to the vessel wall, and extravasate 7 .…”