Pancreatic cancer cells exchange ribosomes through tunneling nanotubes

Abstract

SUMMARYPancreatic 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.HighlightsPDAC cells derived from tumor biopsy samples form tunneling nanotubes in 2D cultureFormation of tunneling nanotubes is stimulated by gemcitabine5.8S ribosomal RNA is transferred in PDAC via activated tunneling nanotubesPolyadenylated RNA is present in tunneling nanotubesRibosomal components are detected in activated tunneling nanotubesPDAC cells exchange assembled ribosomes via tunneling nanotubesRibosomes are transferred via TNTs to recipient cells, incorporated into ribosomes