The role of CXCR3/LRP1 cross-talk in the invasion of primary brain tumors

Kevin Boyé, Nadège Pujol, Isabel Alves, Ya-Ping Chen, Thomas Daubon, Yi-Zong Lee, Stephane Dedieu, Marion Constantin, Lorenzo Bello, Marco Rossi, Rolf Bjerkvig, Shih-Che Sue, Andreas Bikfalvi () and Clotilde Billottet ()
Additional contact information
Kevin Boyé: INSERM U1029
Nadège Pujol: INSERM U1029
Isabel Alves: CBMN
Ya-Ping Chen: NTHU
Thomas Daubon: INSERM U1029
Yi-Zong Lee: NTHU
Stephane Dedieu: Université de Reims Champagne-Ardenne
Marion Constantin: INSERM U1029
Lorenzo Bello: Humanitas Resarch Hospital
Marco Rossi: Humanitas Resarch Hospital
Rolf Bjerkvig: University of Bergen
Shih-Che Sue: NTHU
Andreas Bikfalvi: INSERM U1029
Clotilde Billottet: INSERM U1029

Nature Communications, 2017, vol. 8, issue 1, 1-20

Abstract: Abstract CXCR3 plays important roles in angiogenesis, inflammation, and cancer. However, the precise mechanism of regulation and activity in tumors is not well known. We focused on CXCR3-A conformation and on the mechanisms controlling its activity and trafficking and investigated the role of CXCR3/LRP1 cross talk in tumor cell invasion. Here we report that agonist stimulation induces an anisotropic response with conformational changes of CXCR3-A along its longitudinal axis. CXCR3-A is internalized via clathrin-coated vesicles and recycled by retrograde trafficking. We demonstrate that CXCR3-A interacts with LRP1. Silencing of LRP1 leads to an increase in the magnitude of ligand-induced conformational change with CXCR3-A focalized at the cell membrane, leading to a sustained receptor activity and an increase in tumor cell migration. This was validated in patient-derived glioma cells and patient samples. Our study defines LRP1 as a regulator of CXCR3, which may have important consequences for tumor biology.

Date: 2017
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01686-y

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DOI: 10.1038/s41467-017-01686-y

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