2. Academic Validation
  3. The role of CXCR3/LRP1 cross-talk in the invasion of primary brain tumors

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

  • Nat Commun. 2017 Nov 17;8(1):1571. doi: 10.1038/s41467-017-01686-y.
Kevin Boyé 1 2,  Nadège Pujol 1 2,  Isabel D Alves 3,  Ya-Ping Chen 4,  Thomas Daubon 1 2 5 6,  Yi-Zong Lee 4,  Stephane Dedieu 7,  Marion Constantin 1 2,  Lorenzo Bello 8,  Marco Rossi 8,  Rolf Bjerkvig 5 6,  Shih-Che Sue 4,  Andreas Bikfalvi 9 10,  Clotilde Billottet 11 12
Affiliations

Affiliations

  • 1 INSERM U1029, Pessac, 33615, France.
  • 2 Université de Bordeaux, Pessac, 33615, France.
  • 3 CBMN, UMR 5248 CNRS, Pessac, 33615, France.
  • 4 Institute of Bioinformatics and Structural Biology, NTHU, Hsinchu, 30055, Taiwan.
  • 5 K.G. Jebsen Brain Tumour Research Centre, Department of Biomedicine, University of Bergen, Bergen, 5009, Norway.
  • 6 Department of Oncology, Luxembourg Institute of Health, Luxembourg, L-1526, Luxembourg.
  • 7 CNRS UMR 7369 MEDyC, Université de Reims Champagne-Ardenne, Reims, 51687, France.
  • 8 Neurosurgical Oncology Unit, Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Humanitas Resarch Hospital, Milan, 20089, Italy.
  • 9 INSERM U1029, Pessac, 33615, France. [email protected].
  • 10 Université de Bordeaux, Pessac, 33615, France. [email protected].
  • 11 INSERM U1029, Pessac, 33615, France. [email protected].
  • 12 Université de Bordeaux, Pessac, 33615, France. [email protected].
PMID: 29146996 DOI: 10.1038/s41467-017-01686-y
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.

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