Glycosaminoglycans as Tools to Decipher the Platelet Tumor Cell Interaction: A Focus on P-Selectin.

Abstract

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.

• Authors: Svenja Schwarz, Lukas Maria Gockel, Annamaria Naggi, Uri Barash, Martina Gobec, Gerd Bendas, Martin Schlesinger
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 25 Issue 5 (Feb 26 2020) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 32110917 (Publication Type: Journal Article)

Chemical References

• Glycosaminoglycans
• P-Selectin
• Heparin

Topics

• Blood Platelets (drug effects, pathology)
• Breast Neoplasms (pathology)
• Cell Communication (drug effects)
• Cell Line, Tumor
• Cell Shape (drug effects)
• Cytoplasmic Granules (drug effects, metabolism)
• Glycosaminoglycans (pharmacology)
• Heparin (pharmacology)
• Humans
• Neoplasms (pathology)
• P-Selectin (metabolism)
• Platelet Activation (drug effects)
• Platelet Aggregation (drug effects)
• Signal Transduction (drug effects)