Ceron-Hernandez Jorge, Martinez-Navajas Gonzalo, Sanchez-Manas Jose Manuel, Molina María Pilar, Xie Jiajun, Aznar-Peralta Inés, Garcia-Diaz Abel, Perales Sonia, Torres Carolina, Serrano Maria J, Real Pedro J
Gene Regulation, Stem Cells and Development Group, GENyO, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research, Avenida de la Ilustración 114, 18016 Granada, Spain.
Liquid Biopsies and Cancer Interception Group, PTS, Granada GENyO, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research, Avenida de la Ilustración 114, 18016 Granada, Spain.
Int J Mol Sci. 2025 Apr 1;26(7):3264. doi: 10.3390/ijms26073264.
In the tumor context, platelets play a significant role in primary tumor progression, dissemination and metastasis. Analysis of this interaction in various cancers, such as non-small cell lung cancer (NSCLC), demonstrate that platelets can both transfer and receive biomolecules (e.g. RNA and proteins) to and from the tumor at different stages, becoming tumor-educated platelets. To investigate how platelets are able to transfer oncogenic material, we developed in vitro platelet-like particles (PLPs), from a differentiated MEG-01 cell line, that stably carry RNA and protein of the KRAS oncogene in fusion with GFP. We co-cultured these PLPs with NSCLC H1975 tumor cells to assess their ability to transfer this material. We observed that the generated platelets were capable of stably expressing the oncogene and transferring both its RNA and protein forms to tumor cells using qPCR and imaging techniques. Additionally, we found that coculturing PLPs loaded with GFP-KRAS with tumor cells increased their proliferative capacity at specific PLP concentrations. In conclusion, our study successfully engineered an MEG-01 cell line to produce PLPs carrying oncogenic GFP-KRAS simulating the tumor microenvironment, demonstrating the efficient transfer of this oncogene to tumor cells and its significant impact on enhancing proliferation.
在肿瘤环境中，血小板在原发性肿瘤进展、扩散和转移中发挥着重要作用。对各种癌症（如非小细胞肺癌（NSCLC））中这种相互作用的分析表明，血小板在不同阶段既能向肿瘤传递生物分子（如RNA和蛋白质），也能从肿瘤接收生物分子，从而成为受过肿瘤教育的血小板。为了研究血小板如何能够传递致癌物质，我们从分化的MEG - 01细胞系中开发了体外血小板样颗粒（PLP），其稳定携带与绿色荧光蛋白（GFP）融合的KRAS癌基因的RNA和蛋白质。我们将这些PLP与NSCLC H1975肿瘤细胞共培养，以评估它们传递这种物质的能力。我们观察到，通过定量聚合酶链反应（qPCR）和成像技术，生成的血小板能够稳定表达癌基因，并将其RNA和蛋白质形式传递给肿瘤细胞。此外，我们发现将负载有GFP - KRAS的PLP与肿瘤细胞共培养，在特定PLP浓度下会增加它们的增殖能力。总之，我们的研究成功地改造了MEG - 01细胞系，以产生携带致癌性GFP - KRAS的PLP，模拟肿瘤微环境，证明了这种癌基因向肿瘤细胞的有效传递及其对增强增殖的显著影响。
