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

Author

Listed:
  • Kevin Boyé

    (INSERM U1029
    Université de Bordeaux)

  • Nadège Pujol

    (INSERM U1029
    Université de Bordeaux)

  • Isabel Alves

    (CBMN)

  • Ya-Ping Chen

    (NTHU)

  • Thomas Daubon

    (INSERM U1029
    Université de Bordeaux
    University of Bergen
    Luxembourg Institute of Health)

  • Yi-Zong Lee

    (NTHU)

  • Stephane Dedieu

    (Université de Reims Champagne-Ardenne)

  • Marion Constantin

    (INSERM U1029
    Université de Bordeaux)

  • Lorenzo Bello

    (Humanitas Resarch Hospital)

  • Marco Rossi

    (Humanitas Resarch Hospital)

  • Rolf Bjerkvig

    (University of Bergen
    Luxembourg Institute of Health)

  • Shih-Che Sue

    (NTHU)

  • Andreas Bikfalvi

    (INSERM U1029
    Université de Bordeaux)

  • Clotilde Billottet

    (INSERM U1029
    Université de Bordeaux)

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.

Suggested Citation

  • 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 Bikfa, 2017. "The role of CXCR3/LRP1 cross-talk in the invasion of primary brain tumors," Nature Communications, Nature, vol. 8(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01686-y
    DOI: 10.1038/s41467-017-01686-y
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