嘌呤能信号在血管内皮功能中起着至关重要的作用。特别是，离子型 P2X 受体 (P2XR) 参与各种细胞内途径，内皮细胞 (EC) 通过这些途径适应外部刺激。然而，人们对 P2XR 在癌变过程中对血管重塑的影响知之甚少。我们之前证明，高嘌呤能刺激会损害肿瘤源性内皮细胞（TEC）的迁移表型，但不会损害正常 EC 的迁移表型。由于P2XR对不同的物理和化学因素敏感，我们研究了肿瘤微环境（TME）对健康EC的影响，以验证癌细胞通过嘌呤能信号调节影响内皮迁移表型的能力。更具体地说，我们专注于两种不同类型的 TME 对 P2XR 的调节，模拟乳腺癌和胰腺癌环境，它们在血管化和组成方面表现出截然不同的特征。 ECs 对两种癌细胞类型的调节诱导了一些最具代表性的 P2XR 的显着上调。然而，只有用 MCF-7 细胞而不是 PANC-1 细胞进行调节才能改变正常 EC 的迁移表型，支持 P2XR 介导的细胞迁移抑制。两种癌细胞之间观察到的差异可能是由于它们不同的增殖潜力以及随后不同的细胞外 pH 值造成的。此外，与我们之前的一些数据一致，P2XR 诱导的 EC 迁移抑制似乎与钙信号无关，因为条件 EC 没有显示出嘌呤能激动剂引起的持久反应的任何变化。总的来说，我们的数据强调了 TME 对 P2RX 的显着调节，强化了这样的假设：嘌呤能信号传导可能在癌发生过程中的血管重塑中发挥核心作用。然而，这种调节的上游和下游分子途径仍有待阐明。版权所有 © 2024。

Purinergic signaling plays a crucial role in vascular endothelium functions. In particular, ionotropic P2X receptors (P2XRs) are engaged in various intracellular pathways through which endothelial cells (ECs) adapt to external stimuli. However, very little is known about the impact of P2XRs on vascular remodeling during carcinogenesis. We previously demonstrated that high purinergic stimulation impairs the migratory phenotype of tumor-derived endothelial cells (TECs) but not of normal ECs. Since P2XRs are sensitive to different physical and chemical factors, we investigated the impact of tumor microenvironment (TME) on healthy ECs to verify the ability of cancer cells to affect endothelial migratory phenotype through purinergic signaling tuning. More specifically, we focused on P2XR modulation by two different types of TME, mimicking breast and pancreas cancer milieux, which show very different features in terms of vascularization and composition. ECs conditioning with both cancer cell types induced a significant upregulation of some of the most represented P2XR. However, only conditioning with MCF-7 cells and not that with PANC-1 cells was able to alter the migratory phenotype of normal ECs supporting a P2XR-mediated inhibition of cell migration. The differences observed between the two cancer cells could be due to their different proliferative potential and the subsequent different extracellular pH. In addition, in agreement with some of our previous data, the P2XR-induced inhibition of EC migration seems to be independent of calcium signals, as conditioned ECs didn't reveal any changes in the long-lasting responses evoked by purinergic agonists. Collectively, highlighting a significant P2RX modulation by TME, our data strengthen the hypothesis that purinergic signaling may play a central role in vascular remodeling during carcinogenesis. However, the molecular routes upstream and downstream of this modulation remain to be elucidated.Copyright © 2024.