Background: Pancreatic ductal adenocarcinoma (PDAC) is considered as one of the deadliest types of cancer. Tunnelling nanotubes (TNTs) are thin, membranous, intercellular communication structuresobserved in normal and cancer cells, where they mediate the exchange of intracellular material and promote cell fitness, cancer spread and treatment resistance. Results: PDAC cells increase the formation of TNTs upon exposure to gemcitabine. In the PANC-1 cell line and in tumour explants from patients, we observe polyadenylated mRNA, 5.8S rRNA, ribosomal proteins and assembled 80S ribosomes within the TNTs. Using HaloTag-labelled small ribosomal subunit component RPS9 we demonstrate the transport of ribosomes via TNTs into acceptor cells. Conclusions: PDAC cells can exchange components of the translational machinery, including mRNA, which may contribute to the resistance to therapy, highlighting the potential of targeting TNT dynamics as a therapeutic approach for PDAC.Competing Interest StatementThe authors have declared no competing interest.Footnotes* We added negative controls for several experiments (in supplementary figures and in figure 2E) and a flow cytometry experiment in figure 3F. The text was substantially revised in all sections.* https://github.com/trnkaj/ribosomes...

Pancreatic cancer cells exchange ribosomes through tunneling nanotubes

10.1101/2024.06.06.597772