Pancreatic ductal adenocarcinoma is characterized by a dense stromal or desmoplastic reaction which is caused by pancreatic stellate cells (PSCs). PSCs and cancer cells mutually active each other, thus highlighting the importance of the tumor microenvironment in promoting local tumor growth, metastatic spread and increasing resistance to chemo- and radiation therapy.

We postulate that PSCs are activated and guided by chemo-attractant gradients from the cancer cells. This response leads to the initialization of signaling pathways involving intracellular Ca²⁺ transients mediated by TRPC channels. These have already been linked to cell migration and chemotaxis in other cell types. We therefore investigated the role of TRPC1 and TRPC6 in PSCs isolated from TRPC1^-/- and TRPC6^-/- mice. Using time-lapse video microscopy we monitored the chemokinetic response of PSCs in 3D matrices and the chemotactic response in 2D Ibidi slides to PDGF.

Under control conditions the phenotype of TRPC6^-/- PSCs was changed, showing reduced migration speed compared to WT PSCs both in 2D and 3D environments. Migration speed of TRPC1^-/- PSCs did not differ from speed of WT cells. The defect in migration of TRPC6^-/- PSCs could be overcome by PDGF stimulation. In presence of PDGF the distance covered during the course of the experiment almost doubled and PSCs efficiently chemotax in a gradient of PDGF. This was also the case in TRPC1^-/- PSCs.

We can therefore conclude that TRPC6 channels play a role in PSC migration and may have an effect through other stimulatory pathways than PDGF.