Posgrado en Ciencias Biológicas, UNAM, Mexico City 04510, Mexico.
Epigenetics Laboratory (2), Instituto Nacional de Medicina Genómica (INMEGEN), Mexico City 14160, Mexico.
Int J Mol Sci. 2022 Sep 28;23(19):11438. doi: 10.3390/ijms231911438.
Pancreatic cancer is a pathology with a high mortality rate since it is detected at advanced stages, so the search for early-stage diagnostic biomarkers is essential. Liquid biopsies are currently being explored for this purpose and educated platelets are a good candidate, since they are known to present a bidirectional interaction with tumor cells. In this work, we analyzed the effects of platelets on cancer cells' viability, as determined by MTT, migration using transwell assays, clonogenicity in soft agar and stemness by dilution assays and stem markers' expression. We found that the co-culture of platelets and pancreatic cancer cells increased the proliferation and migration capacity of BXCP3 cells, augmented clonogenicity and induced higher levels of Nanog, Sox2 and Oct4 expression. As platelets can provide horizontal transfer of microRNAs, we also determined the differential expression of miRNAs in platelets obtained from a small cohort of pancreatic cancer patients and healthy subjects. We found clear differences in the expression of several miRNAs between platelets of patients with cancer healthy subjects. Moreover, when we analyzed microRNAs from the platelets of the pancreatic juice and blood derived from each of the cancer patients, interestingly we find differences between the blood- and pancreatic juice-derived platelets suggesting the presence of different subpopulations of platelets in cancer patients, which warrant further analysis.
胰腺癌的死亡率很高,因为它在晚期才被发现,因此寻找早期诊断生物标志物至关重要。目前正在探索液体活检来实现这一目标,有教育意义的血小板是一个很好的候选者,因为已知它们与肿瘤细胞之间存在双向相互作用。在这项工作中,我们通过 MTT 分析、transwell 迁移分析、软琼脂克隆形成分析和稀释分析以及干细胞标志物表达分析来研究血小板对癌细胞活力的影响。我们发现血小板和胰腺癌细胞的共培养增加了 BXCP3 细胞的增殖和迁移能力,增强了克隆形成能力,并诱导了更高水平的 Nanog、Sox2 和 Oct4 表达。由于血小板可以提供 microRNAs 的水平转移,我们还确定了从小部分胰腺癌患者和健康受试者中获得的血小板中 microRNAs 的差异表达。我们发现癌症患者和健康受试者血小板中几种 microRNAs 的表达存在明显差异。此外,当我们分析每个癌症患者的胰腺液和血液中的血小板 microRNAs 时,有趣的是,我们发现血液和胰腺液来源的血小板之间存在差异,这表明癌症患者中存在不同的血小板亚群,这需要进一步分析。