VDR signaling inhibits cancer-associated-fibroblasts’ release of exosomal miR-10a-5p and limits their supportive effects on pancreatic cancer cells

We read with great interest the recent publication by Ferrer-Mayorga et al ,1 concerning Vitamin D receptor (VDR) signalling’s impacts on cancer-associated fibroblasts (CAFs) in colorectal cancer (CRC). In line with one previous publication regarding VDR in pancreatic cancer (PC),2 activation of VDR signalling in stromal fibroblasts predicts a favourable clinical outcome in CRC. Both reports set the concept in principle that VDR agonists can be explored as a therapy against tumor-associated stroma in PC and CRC. However, detailed mechanisms involved in VDR’s regulation of tumor-stroma crosstalk remained to be elucidated. Recent publications identified exosomal miRNAs as critical mediators for cellular communication. In this study, we aimed to investigate whether exosomal miRNAs were implicated in VDR’s regulation against the protumoural activity of CAFs. Three immortalised CAF cell lines were generated from PC patients following the protocol reported previously.3 Exosomes released by CAFs were labelled with fluorescent dye 1,1’-dioctadecyl-3,3,3’,3’-tetramethylindocarbocyanine perchlorate (DiI) and incubated with PC cell lines (PANC-1 and SW1990) for 24 hours. Analysis using fluorescence microscopy (figure 1A) and flow cytometry (figure …