Glycosaminoglycans as tools to decipher the platelet tumor cell interaction : a focus on P-selectin

Schwarz, Svenja (avtor), Gockel, Lukas Maria (avtor), Naggi, Annamaria (avtor), Barash, Uri (avtor), Gobec, Martina (avtor), Bendas, Gerd (avtor), Schlesinger, Martin (avtor)

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.

• Jezik: Angleški jezik
• Ključne besede: 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
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2020
• Št. strani: 16 str.
• Številčenje: Vol. 25, iss. 5, art. 1039
• PID: 20.500.12556/RUL-133623
• UDK: 611.1:616-006:616-033.2
• ISSN pri članku: 1420-3049
• DOI: 10.3390/molecules25051039
• COBISS.SI-ID: 4888177
• Datum objave v RUL: 06.12.2021

Gradivo je del revije

• Naslov: Molecules
• Skrajšan naslov: Molecules
• Založnik: MDPI
• ISSN: 1420-3049
• COBISS.SI-ID: 18462981

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.
• Začetek licenciranja: 01.03.2020

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: angiogeneza, tumorji, metastaziranje, heparin, P-selektin, glikozaminoglikani

Projekti

• Financer: Drugi - Drug financer ali več financerjev
• Program financ.: Kirstin Diehl Stiftung