GPCRs expressed by cancer-associated fibroblasts are potential therapeutic targets in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense fibrotic stromal matrix (desmoplasia) composed of activated fibroblasts (PFs) /stellate cells (PSCs), immune/ inflammatory cells and other cell types. Considerable evidence implicates this unique tumor microenvironment, and in particular its stromal cells, as a key mediator of PDAC progression and drug resistance. The tumor stroma may thus be a target for the treatment of PDAC. Pancreatic cancer-associated fibroblasts (CAFs), myofibroblast-like cells, thought to be derived from PSCs and PFs, produce extracellular matrix proteins and, are responsible for the desmoplasia in PDAC. Blocking the activity of CAFs may thus be a means to improve the therapy and prognosis of PDAC. We hypothesized that G protein-coupled receptors (GPCRs) expressed by pancreatic CAFs may be potential therapeutic targets for PDAC. As an initial effort to test this hypothesis, we used an unbiased approach, Taqman GPCR arrays that can assess ~360 non-chemosensory GPCRs...