ǂa ǂfocus on P-selectin
Svenja Schwarz (Avtor), Lukas Maria Gockel (Avtor), Annamaria Naggi (Avtor), Uri Barash (Avtor), Martina Gobec (Avtor), Gerd Bendas (Avtor), Martin Schlesinger (Avtor)

Povzetek

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.

Ključne besede

heparin;P-selektin;glikozaminoglikani;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;

Podatki

Jezik: Angleški jezik
Leto izida:
Tipologija: 1.01 - Izvirni znanstveni članek
Organizacija: UL FFA - Fakulteta za farmacijo
UDK: 611.1:616-006:616-033.2
COBISS: 4888177 Povezava se bo odprla v novem oknu
ISSN: 1420-3049
Št. ogledov: 131
Št. prenosov: 60
Ocena: 0 (0 glasov)
Metapodatki: JSON JSON-RDF JSON-LD TURTLE N-TRIPLES XML RDFA MICRODATA DC-XML DC-RDF RDF

Ostali podatki

Sekundarni jezik: Slovenski jezik
Sekundarne ključne besede: Angiogeneza;Tumorji;Metastaziranje;
Vrsta dela (COBISS): Članek v reviji
Strani: str. 1-16
Letnik: ǂVol. ǂ25
Zvezek: ǂiss. ǂ5
Čas izdaje: 2020
DOI: 10.3390/molecules25051039
ID: 14054295