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

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

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.

• Language: English
• Keywords: 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
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2020
• Number of pages: 16 str.
• Numbering: Vol. 25, iss. 5, art. 1039
• PID: 20.500.12556/RUL-133623
• UDC: 611.1:616-006:616-033.2
• ISSN on article: 1420-3049
• DOI: 10.3390/molecules25051039
• COBISS.SI-ID: 4888177
• Publication date in RUL: 06.12.2021

Record is a part of a journal

• Title: Molecules
• Shortened title: Molecules
• Publisher: MDPI
• ISSN: 1420-3049
• COBISS.SI-ID: 18462981

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 01.03.2020

Secondary language

• Language: Slovenian
• Keywords: angiogeneza, tumorji, metastaziranje, heparin, P-selektin, glikozaminoglikani

Projects

• Funder: Other - Other funder or multiple funders
• Funding programme: Kirstin Diehl Stiftung