Inhibition of CX3CR1 reduces cell motility and viability in pancreatic adenocarcinoma epithelial cells |
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| Authors: | Matthew C Stout Shilpa Narayan Emily S Pillet Joseph M Salvino Paul M Campbell |
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| Institution: | 1. Department of Pharmacology & Physiology, College of Medicine, Drexel University, 245 North 15th Street, MS 488, Philadelphia, PA 19102, USA;2. Molecular and Cellular Oncogenesis Program, Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA |
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| Abstract: | Increased expression of the chemokine CX3CL1 and its sole receptor, CX3CR1 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 CX3CL1, and have developed small molecule inhibitors against the CX3CR1 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 CX3CL1 exposure, and that antagonism of CX3CR1 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. |
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| Keywords: | Pancreatic cancer Invasion Metastasis Chemokine receptors Targeted therapy |
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