Pancreatic cancer cells exchange ribosomes through tunneling nanotubes

SUMMARY Pancreatic ductal adenocarcinoma (PDAC) is recognized as one of the most lethal types of cancer. Tunneling nanotubes (TNTs) are thin membranous intercellular communications, which allow cells to exchange intracellular material and promote cell fitness. We show here that PDAC cells increase the formation of TNTs upon exposure to gemcitabine and that these TNTs contain ribosomal components. In the PANC-1 cell line and in PDAC explants obtained from patient biopsies, we observe polyadenylated RNA and assembled 80S ribosomes within the TNTs, indicating the possibility of an intercellular transfer of translationally active ribosomes. Using cells with labelled small ribosomal subunits (40S), we demonstrate active transport of the ribosomal subunit via TNTs to recipient cells. Our results show that 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. Highlights PDAC cells derived from tumor biopsy samples form tunneling nanotubes in 2D culture Formation of tunneling nanotubes is stimulated by gemcitabine 5.8S ribosomal RNA is transferred in PDAC via activated tunneling nanotubes Polyadenylated RNA is present in tunneling nanotubes Ribosomal components are detected in activated tunneling nanotubes PDAC cells exchange assembled ribosomes via tunneling nanotubes Ribosomes are transferred via TNTs to recipient cells, incorporated into ribosomes