Inhibition of CX 3 CR1 reduces cell motility and viability in pancreatic adenocarcinoma epithelial cells.

Increased expression of the chemokine CX3 CL1 and its sole receptor, CX3 CR1 have been correlated with poor pancreatic cancer patient survival and time to recurrence, as well as with pancreatic perineural invasion. We have previously shown that metastasis of prostate and breast cancer is in part driven by CX3 CL1, and have developed small molecule inhibitors against the CX3 CR1 receptor that diminish metastatic burden. Here we ask if inhibition of this chemokine receptor affects the phenotype of PDAC tumor cells. Our findings demonstrate that motility, invasion, and contact-independent growth of PDAC cells all increase following CX3 CL1 exposure, and that antagonism of CX3 CR1 by the inhibitor JMS-17-2 reduces each of these phenotypes and correlates with a downregulation of AKT phosphorylation. These data suggest that PDAC tumor cell migration and growth, elements critical in metastatic progression, may susceptible to pharmacologic intervention.