Glycosaminoglycans as Tools to Decipher the Platelet Tumor Cell Interaction: A Focus on P-Selectin
| Autor: | Annamaria Naggi, Gerd Bendas, Martin Schlesinger, Martina Gobec, Svenja Schwarz, Uri Barash, Lukas Maria Gockel |
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| Rok vydání: | 2020 |
| Předmět: |
P-selectin
Platelet Aggregation Angiogenesis Pharmaceutical Science Cell Communication Analytical Chemistry 0302 clinical medicine Neoplasms Drug Discovery Platelet hexasaccharide heparin fragment Glycosaminoglycans 0303 health sciences Chemistry low molecular weight heparin Heparin unfractionated heparin Extravasation 2-O-desulfated heparin P-Selectin Coagulation Chemistry (miscellaneous) 030220 oncology & carcinogenesis platelets Molecular Medicine medicine.drug Signal Transduction Blood Platelets medicine.drug_class platelet secretion Low molecular weight heparin Breast Neoplasms Cytoplasmic Granules RO-heparin Article lcsh:QD241-441 03 medical and health sciences lcsh:Organic chemistry decasaccharide heparin fragment Cell Line Tumor medicine Humans Platelet activation Physical and Theoretical Chemistry Cell Shape 030304 developmental biology tumor metastasis Organic Chemistry Platelet Activation 2-o-desulfated heparin Cancer research |
| Zdroj: | Molecules Molecules, Vol 25, Iss 5, p 1039 (2020) Volume 25 Issue 5 |
| ISSN: | 1420-3049 |
| Popis: | Tumor cell&ndash 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. |
| Databáze: | OpenAIRE |
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