In circulation, cancer cells induce platelet activation, leading to the formation of a cancer cell‐encircling platelet cloak which facilitates each step of the metastatic cascade. Since cancer patients treated with the anticoagulant heparin showed reduced metastasis rates and improved survival, it is supposed that heparin suppresses the cloak's formation by inhibiting the interaction between platelet's adhesion molecule P‐selectin with its ligands on cancer cells. To quantify this heparin effect, we developed a single‐cell force spectroscopy approach and quantified the adhesion (maximum adhesion force [F_A] and detachment work [W_D]) between platelets and human non‐small cell lung cancer cells (A549). A configuration was used in which A549 cells were glued to tipless cantilevers and force‐distance (F‐D) curves were recorded on a layer of activated platelets. The concentration‐response relationship was determined for heparin at concentrations between 1 and 100 U/mL. Sigmoid dose‐response fit revealed half‐maximal inhibitory concentration (IC₅₀) values of 8.01 U/mL (F_A) and 6.46 U/mL (W_D) and a maximum decrease of the adhesion by 37.5% (F_A) and 38.42% (W_D). The effect of heparin on P‐selectin was tested using anti‐P‐selectin antibodies alone and in combination with heparin. Adding heparin after antibody treatment resulted in an additional reduction of 9.52% (F_A) and 7.12% (W_D). Together, we quantified heparin's antimetastatic effect and proved that it predominantly is related to the blockage of P‐selectin. Our approach represents a valuable method to investigate the adhesion of platelets to cancer cells and the efficiency of substances to block this interaction.

中文翻译：

---

通过单细胞力谱法定量肝素的抗转移作用。

在循环中，癌细胞诱导血小板活化，导致形成包围癌细胞的血小板披风，从而促进转移级联的每一步。由于接受抗凝肝素治疗的癌症患者显示出转移率降低和存活率提高，因此推测肝素通过抑制血小板粘附分子 P-选择素与其在癌细胞上的配体之间的相互作用来抑制斗篷的形成。_{为了量化这种肝素效应，我们开发了一种}单细胞力谱方法并量化了粘附（最大粘附力 [ FA ] 和脱离功 [ W _D]）在血小板和人非小细胞肺癌细胞（A549）之间。使用了一种配置，其中将 A549 细胞粘在无尖端的悬臂上，并在一层活化的血小板上记录力-距离 (F-D) 曲线。确定浓度在 1 到 100 U/mL 之间的肝素的浓度-反应关系。Sigmoid 剂量反应拟合显示半数最大抑制浓度 (IC ₅₀ ) 值为 8.01 U/mL ( FA ₎和 6.46 U/mL ( W _D )，粘连最大降低 37.5% ( FA ₎和 38.42 % ₍宽）。单独使用抗 P-选择素抗体和联合肝素测试肝素对 P-选择素的影响。在抗体处理后添加肝素导致额外减少 9.52% ( FA ₎和 7.12% ( W _D )。我们一起量化了肝素的抗转移作用，并证明它主要与 P-选择素的阻断有关。我们的方法代表了一种有价值的方法来研究血小板与癌细胞的粘附以及物质阻止这种相互作用的效率。