Petry Julie, Mai Han, Shoykhet Maria, Bashiri Dezfouli Ali, Wollenberg Barbara
Department of Otorhinolaryngology, Head and Neck Surgery, School of Medicine and Health, TUM University Hospital, Technical University of Munich, Munich, Germany.
Front Pharmacol. 2025 Jun 5;16:1546157. doi: 10.3389/fphar.2025.1546157. eCollection 2025.
Platelets, traditionally recognized for their role in hemostasis, have increasingly been implicated in cancer progression, including head and neck squamous cell carcinoma (HNSCC). Beyond releasing growth factors and chemokines, platelets modulate leukocyte-mediated proinflammatory responses and effector functions through direct or indirect contact. These processes promote tumor cell proliferation, survival, epithelial to mesenchymal transition (EMT) and extravasation. Consequently, targeting platelet-leukocyte aggregate (PLA) formation represents a promising pharmacological strategy to interfere with platelet-mediated pro-tumorigenic effects. 1,8-cineole, a plant-derived metabolite found in several botanical sources, has shown potent anti-platelet effects through modulation of the adenosine A receptor signaling. However, its influence on PLA formation has not been investigated.
In this study, we analyzed platelet activation and PLA formation in HNSCC patients compared to healthy donors. A co-culture system combined with blocking antibodies was employed to elucidate the mechanisms of PLA formation. Moreover, the pharmacological effects of 1,8-cineole were compared with those of conventional anti-platelet drugs.
The results revealed elevated P-selectin expression and enhanced PLA formation in HNSCC patients. PLA formation was predominantly mediated through P-selectin-PSGL-1 interactions. studies demonstrated that 1,8-cineole significantly reduced PLA formation by inhibiting P-selectin expression on platelets. Notably, traditional anti-platelet agents did not significantly inhibit PLA formation, despite effectively reducing platelet aggregation.
These findings identify a pharmacological effect of 1,8-cineole in disrupting platelet-leukocyte interactions via suppression of the P-selectin-PSGL-1 axis. This suggests that 1,8-cineole offers potential pharmacological benefits in mitigating platelet-mediated inflammation and tumor progression.
血小板传统上被认为在止血过程中发挥作用，但其在癌症进展中的作用越来越受到关注，包括头颈部鳞状细胞癌（HNSCC）。除了释放生长因子和趋化因子外，血小板还通过直接或间接接触调节白细胞介导的促炎反应和效应功能。这些过程促进肿瘤细胞增殖、存活、上皮-间质转化（EMT）和外渗。因此，靶向血小板-白细胞聚集体（PLA）的形成是一种有前景的药理学策略，可干扰血小板介导的促肿瘤效应。1,8-桉叶素是一种在多种植物来源中发现的植物衍生代谢产物，已显示出通过调节腺苷A受体信号传导发挥强大的抗血小板作用。然而，其对PLA形成的影响尚未得到研究。
在本研究中，我们分析了HNSCC患者与健康供体相比的血小板活化和PLA形成情况。采用共培养系统结合阻断抗体来阐明PLA形成的机制。此外，将1,8-桉叶素的药理作用与传统抗血小板药物的药理作用进行了比较。
结果显示HNSCC患者的P-选择素表达升高，PLA形成增强。PLA的形成主要通过P-选择素-PSGL-1相互作用介导。研究表明，1,8-桉叶素通过抑制血小板上P-选择素的表达显著减少了PLA的形成。值得注意的是，传统抗血小板药物尽管有效降低了血小板聚集，但并未显著抑制PLA的形成。
这些发现确定了1,8-桉叶素通过抑制P-选择素-PSGL-1轴破坏血小板-白细胞相互作用的药理作用。这表明1,8-桉叶素在减轻血小板介导的炎症和肿瘤进展方面具有潜在的药理益处。
