Ballerini Patrizia, Contursi Annalisa, Bruno Annalisa, Mucci Matteo, Tacconelli Stefania, Patrignani Paola
Center for Advanced Studies and Technology (CAST), Chieti, Italy.
Department of Innovative Technologies in Medicine and Dentistry, Chieti, Italy.
Front Pharmacol. 2022 Mar 3;13:838079. doi: 10.3389/fphar.2022.838079. eCollection 2022.
Colorectal (CRC) and hepatocellular carcinoma (HCC) are associated with chronic inflammation, which plays a role in tumor development and malignant progression. An unmet medical need in these settings is the availability of sensitive and specific noninvasive biomarkers. Their use will allow surveillance of high-risk populations, early detection, and monitoring of disease progression. Moreover, the characterization of specific fingerprints of patients with nonalcoholic fatty liver disease (NAFLD) without or with nonalcoholic steatohepatitis (NASH) at the early stages of liver fibrosis is necessary. Some lines of evidence show the contribution of platelets to intestinal and liver inflammation. Thus, low-dose Aspirin, an antiplatelet agent, reduces CRC and liver cancer incidence and mortality. Aspirin also produces antifibrotic effects in NAFLD. Activated platelets can trigger chronic inflammation and tissue fibrosis via the release of soluble mediators, such as thromboxane (TX) A and tumor growth factor (TGF)-β, and vesicles containing genetic material (including microRNA). These platelet-derived products contribute to cyclooxygenase (COX)-2 expression and prostaglandin (PG)E biosynthesis by tumor microenvironment cells, such as immune and endothelial cells and fibroblasts, alongside cancer cells. Enhanced COX-2-dependent PGE plays a crucial role in chronic inflammation and promotes tumor progression, angiogenesis, and metastasis. Antiplatelet agents can indirectly prevent the induction of COX-2 in target cells by inhibiting platelet activation. Differently, selective COX-2 inhibitors (coxibs) block the activity of COX-2 expressed in the tumor microenvironment and cancer cells. However, coxib chemopreventive effects are hampered by the interference with cardiovascular homeostasis via the coincident inhibition of vascular COX-2-dependent prostacyclin biosynthesis, resulting in enhanced risk of atherothrombosis. A strategy to improve anti-inflammatory agents' use in cancer prevention could be to develop tissue-specific drug delivery systems. Platelet ability to interact with tumor cells and transfer their molecular cargo can be employed to design platelet-mediated drug delivery systems to enhance the efficacy and reduce toxicity associated with anti-inflammatory agents in these settings. Another peculiarity of platelets is their capability to uptake proteins and transcripts from the circulation. Thus, cancer patient platelets show specific proteomic and transcriptomic expression profiles that could be used as biomarkers for early cancer detection and disease monitoring.
结直肠癌（CRC）和肝细胞癌（HCC）与慢性炎症相关，慢性炎症在肿瘤发生和恶性进展中起作用。在这些情况下，一个未满足的医学需求是获得敏感且特异的非侵入性生物标志物。它们的使用将有助于对高危人群进行监测、早期检测以及监测疾病进展。此外，有必要对处于肝纤维化早期、有无非酒精性脂肪性肝炎（NASH）的非酒精性脂肪性肝病（NAFLD）患者的特定特征进行描述。一些证据表明血小板对肠道和肝脏炎症有影响。因此，低剂量阿司匹林这种抗血小板药物可降低CRC和肝癌的发病率及死亡率。阿司匹林在NAFLD中也产生抗纤维化作用。活化的血小板可通过释放可溶性介质（如血栓素（TX）A和肿瘤生长因子（TGF）-β）以及含有遗传物质（包括微小RNA）的囊泡来触发慢性炎症和组织纤维化。这些血小板衍生产物有助于肿瘤微环境细胞（如免疫细胞、内皮细胞、成纤维细胞以及癌细胞）中环氧合酶（COX）-2的表达和前列腺素（PG）E的生物合成。增强的COX-2依赖性PGE在慢性炎症中起关键作用，并促进肿瘤进展、血管生成和转移。抗血小板药物可通过抑制血小板活化间接阻止靶细胞中COX-2的诱导。不同的是，选择性COX-2抑制剂（coxibs）可阻断肿瘤微环境和癌细胞中表达的COX-2的活性。然而，coxib的化学预防作用因同时抑制血管COX-2依赖性前列环素的生物合成而干扰心血管稳态，导致动脉粥样血栓形成风险增加而受到阻碍。一种改善抗炎药物在癌症预防中应用的策略可能是开发组织特异性药物递送系统。血小板与肿瘤细胞相互作用并转移其分子货物的能力可用于设计血小板介导的药物递送系统，以提高疗效并降低这些情况下与抗炎药物相关的毒性。血小板的另一个独特之处在于它们有能力从循环中摄取蛋白质和转录本。因此，癌症患者的血小板表现出特定的蛋白质组和转录组表达谱，可作为早期癌症检测和疾病监测的生物标志物。
