Oncogenic Transfer of KRASG12D from Platelet-like Particles to Non-Small Cell Lung Cancer Cells Promotes Proliferation and Increases Drug Resistance

In the tumor context, platelets play a significant role in both 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 differentiated MEG-01 cell line, stably carrying RNA and protein of the KRASG12D oncogene in fusion with GFP. We cocultured 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-KRASG12D with tumor cells increased their proliferative capacity at specific PLPs concentrations. Moreover, cells cocultured with these PLPs showed enhanced survival when treated with the tyrosine kinase inhibitor osimertinib. In conclusion, our study successfully engineered MEG-01 cells to produce PLPs carrying oncogenic GFP-KRASG12D simulating the tumor microenvironment, demonstrating the efficient transfer of this oncogene to tumor cells and its significant impact on enhancing proliferation and drug resistance.