20.500.12556/RUL-133623 Glycosaminoglycans as tools to decipher the platelet tumor cell interaction a focus on P-selectin Tumor cell-platelet interactions are regarded as an initial crucial step in hematogenous metastasis. Platelets protect tumor cells from immune surveillance in the blood, mediate vascular arrest, facilitate tumor extravasation, growth, and finally angiogenesis in the metastatic foci. Tumor cells aggregate platelets in the bloodstream by activation of the plasmatic coagulation cascade and by direct contact formation. Antimetastatic activities of unfractionated or low molecular weight heparin (UFH/LMWH) can undoubtedly be related to attenuated platelet activation, but molecular mechanisms and contribution of contact formation vs. coagulation remain to be elucidated. Using a set of non-anticoagulant heparin derivatives varying in size or degree of sulfation as compared with UFH, we provide insight into the relevance of contact formation for platelet activation. Light transmission aggregometry and ATP release assays confirmed that only those heparin derivatives with P-selectin blocking capacities were able to attenuate breast cancer cell-induced platelet activation, while pentasaccharide fondaparinux was without effects. Furthermore, a role of P-selectin in platelet activation and signaling could be confirmed by proteome profiler arrays detecting platelet kinases. In this study, we demonstrate that heparin blocks tumor cell-induced coagulation. Moreover, we identify platelet P-selectin, which obviously acts as molecular switch and controls aggregation and secretion of procoagulant platelets. RO-heparin 2-O-desulfated heparin hexasaccharide heparin fragment decasaccharide heparin fragment unfractionated heparin low molecular weight heparin platelets P-selectin platelet aggregation platelet secretion tumor metastasis angiogeneza tumorji metastaziranje heparin P-selektin glikozaminoglikani true false true Angleški jezik Slovenski jezik Članek v reviji 2021-12-06 11:39:42 2021-12-06 11:39:50 2022-09-13 03:51:42 0000-00-00 00:00:00 2020 0 0 16 str. iss. 5, art. 1039 Vol. 25 2020 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 611.1:616-006:616-033.2 1420-3049 10.3390/molecules25051039 4888177 RAZ_Schwarz_Svenja_2020.pdf RAZ_Schwarz_Svenja_2020.pdf 1 97FE6722BC5BC1538B7A29059778EC8D 2fcdc0058389c8c5fd8828903739b69fdddaaa6336778573ddaa3e55034d52a3 fe265205-5680-11ec-abdb-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=151833 https://www.mdpi.com/1420-3049/25/5/1039 0 bbf73162-5680-11ec-abdb-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=151832 Fakulteta za farmacijo 0 0 0