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检测肿瘤细胞诱导的血小板聚集和颗粒分泌。

Detection of Tumor Cell-Induced Platelet Aggregation and Granule Secretion.

机构信息

Pharmaceutical Department, University Bonn, Bonn, Germany.

出版信息

Methods Mol Biol. 2021;2294:181-195. doi: 10.1007/978-1-0716-1350-4_13.

Abstract

Hematogenous metastatic spread of cancer is strongly dependent on and triggered by an intensive interplay of tumor cells with platelets. Immediately after entering the blood vascular system, tumor cells are surrounded by a platelet cloak, which protects them physically from shear stress and from attacks by the immune surveillance. Furthermore, tumor cell binding activates platelets, which in turn release growth factors and chemokines to recruit myeloid cells into the platelet/tumor cell microemboli, eventually create a permissive microenvironment in the early metastatic niche. Although the molecular mechanisms of tumor cells to activate platelets appear versatile being a matter of further research, interference with platelet activation turns out to be an attractive target to efficiently inhibit tumor metastasis. Some experimental assays are generally recognized to follow tumor cell-induced platelet activation (TCIPA), which provide an insight into the molecular mechanisms of TCIPA and allow searching for potential inhibitors. In this chapter, we describe the two most prominent experimental assays to follow TCIPA, namely platelet aggregation and platelet granule secretion, experimentally realized by dense granules´ ATP quantification. Although light transmission aggregometry and ATP detection from dense granule secretion are two age-old techniques, they are still highly relevant to provide reliable information concerning platelet activation status since all tumor cell-derived molecular triggers are covered and monitored in the experimental outcome.

摘要

肿瘤的血行转移扩散强烈依赖于并受肿瘤细胞与血小板之间的密集相互作用触发。肿瘤细胞进入血管系统后,立即被血小板包围,这使它们在物理上免受切应力和免疫监视的攻击。此外,肿瘤细胞结合激活血小板,血小板反过来释放生长因子和趋化因子招募髓系细胞进入血小板/肿瘤细胞微栓,最终在早期转移龛位中创造一个许可的微环境。尽管肿瘤细胞激活血小板的分子机制似乎多种多样,这是进一步研究的问题,但干扰血小板激活被证明是有效抑制肿瘤转移的有吸引力的靶点。一些实验方法通常被认为是遵循肿瘤细胞诱导的血小板激活(TCIPA),这为研究 TCIPA 的分子机制提供了深入了解,并允许寻找潜在的抑制剂。在这一章中,我们描述了两种最突出的实验方法来跟踪 TCIPA,即血小板聚集和血小板颗粒分泌,通过致密颗粒的 ATP 定量来实现。虽然透光比浊法聚集和致密颗粒分泌的 ATP 检测是两种古老的技术,但它们仍然高度相关,能够提供有关血小板激活状态的可靠信息,因为所有肿瘤细胞衍生的分子触发因素都在实验结果中得到了覆盖和监测。

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