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Journal article
Inhibition of CX3CR1 reduces cell motility and viability in pancreatic adenocarcinoma epithelial cells
Biochemical and biophysical research communications, v 495(3), pp 2264-2269
15 Jan 2018
PMID: 29274778
Featured in Collection : UN Sustainable Development Goals @ Drexel
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.
• Inhibition of CX3CR1 by the antagonist JMS-17-2 in PDAC cells reduces motility.
• CX3CR1 antagonism inhibits PDAC cell contact-independent colony development.
• CX3CR1 blockade reduces CX3CL1-driven PDAC invasion through extracellular matrix.
• JMS-17-2 shows no toxicity to adherent cells under normal culture conditions.
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Details
- Title
- Inhibition of CX3CR1 reduces cell motility and viability in pancreatic adenocarcinoma epithelial cells
- Creators
- Matthew C. Stout - Drexel UniversityShilpa Narayan - Department of Pharmacology & Physiology, College of Medicine, Drexel University, 245 North 15th Street, MS 488, Philadelphia, PA 19102, USAEmily S. Pillet - Drexel UniversityJoseph M. Salvino - The Wistar InstitutePaul M. Campbell - Department of Pharmacology & Physiology, College of Medicine, Drexel University, 245 North 15th Street, MS 488, Philadelphia, PA 19102, USA
- Publication Details
- Biochemical and biophysical research communications, v 495(3), pp 2264-2269
- Publisher
- Elsevier
- Number of pages
- 6
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000424732400025
- Scopus ID
- 2-s2.0-85039044283
- Other Identifier
- 991021904613504721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Biophysics