Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Campus UNAM-Juriquilla, Querétaro 76230, CP, Mexico.
Int J Mol Sci. 2022 Apr 21;23(9):4585. doi: 10.3390/ijms23094585.
The purinergic system is fundamental in the tumor microenvironment, since it regulates tumor cell interactions with the immune system, as well as growth and differentiation in autocrine-paracrine responses. Here, we investigated the role of the adenosine A2B receptor (A2BR) in ovarian carcinoma-derived cells' (OCDC) properties. From public databases, we documented that high A2BR expression is associated with a better prognostic outcome in ovarian cancer patients. In vitro experiments were performed on SKOV-3 cell line to understand how A2BR regulates the carcinoma cell phenotype associated with cell migration. RT-PCR and Western blotting revealed that the transcript (coding for A2BR) and A2BR were expressed in SKOV-3 cells. Stimulation with BAY-606583, an A2BR agonist, induced ERK1/2 phosphorylation, which was abolished by the antagonist PSB-603. Pharmacological activation of A2BR reduced cell migration and actin stress fibers; in agreement, A2BR knockdown increased migration and enhanced actin stress fiber expression. Furthermore, the expression of E-cadherin, an epithelial marker, increased in BAY-606583-treated cells. Finally, cDNA microarrays revealed the pathways mediating the effects of A2BR activation on SKOV-3 cells. Our results showed that A2BR contributed to maintaining an epithelial-like phenotype in OCDC and highlighted this purinergic receptor as a potential biomarker.
嘌呤能系统在肿瘤微环境中起着基础性作用，因为它调节肿瘤细胞与免疫系统的相互作用，以及自分泌-旁分泌反应中的生长和分化。在这里，我们研究了腺苷 A2B 受体 (A2BR) 在卵巢癌细胞源性细胞 (OCDC) 特性中的作用。从公共数据库中，我们记录到 A2BR 高表达与卵巢癌患者的预后更好相关。在 SKOV-3 细胞系上进行的体外实验，旨在了解 A2BR 如何调节与细胞迁移相关的癌性细胞表型。RT-PCR 和 Western blot 显示 SKOV-3 细胞中表达 转录本（编码 A2BR）和 A2BR。用 A2BR 激动剂 BAY-606583 刺激诱导 ERK1/2 磷酸化，该磷酸化被拮抗剂 PSB-603 所阻断。A2BR 的药理学激活减少了细胞迁移和肌动蛋白应力纤维；与之一致，A2BR 的敲低增加了迁移并增强了肌动蛋白应力纤维的表达。此外，上皮标志物 E-钙黏蛋白的表达在 BAY-606583 处理的细胞中增加。最后，cDNA 微阵列揭示了介导 A2BR 激活对 SKOV-3 细胞影响的途径。我们的结果表明，A2BR 有助于维持 OCDC 中的上皮样表型，并突出了该嘌呤能受体作为潜在的生物标志物。
