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CXCL1 mediates obesity-associated adipose stromal cell trafficking and function in the tumour microenvironment

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  • Tao Zhang

    (The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston)

  • Chieh Tseng

    (The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston)

  • Yan Zhang

    (The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston)

  • Olga Sirin

    (The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston)

  • Paul G. Corn

    (The University of Texas MD Anderson Cancer Center)

  • Elsa M. Li-Ning-Tapia

    (The University of Texas MD Anderson Cancer Center)

  • Patricia Troncoso

    (The University of Texas MD Anderson Cancer Center)

  • John Davis

    (The University of Texas MD Anderson Cancer Center)

  • Curtis Pettaway

    (The University of Texas MD Anderson Cancer Center)

  • John Ward

    (The University of Texas MD Anderson Cancer Center)

  • Marsha L. Frazier

    (The University of Texas MD Anderson Cancer Center)

  • Christopher Logothetis

    (The University of Texas MD Anderson Cancer Center)

  • Mikhail G. Kolonin

    (The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston)

Abstract

White adipose tissue (WAT) overgrowth in obesity is linked with increased aggressiveness of certain cancers. Adipose stromal cells (ASCs) can become mobilized from WAT, recruited by tumours and promote cancer progression. Mechanisms underlying ASC trafficking are unclear. Here we demonstrate that chemokines CXCL1 and CXCL8 chemoattract ASC by signalling through their receptors, CXCR1 and CXCR2, in cell culture models. We further show that obese patients with prostate cancer have increased epithelial CXCL1 expression. Concomitantly, we observe that cells with ASC phenotype are mobilized and infiltrate tumours in obese patients. Using mouse models, we show that the CXCL1 chemokine gradient is required for the obesity-dependent tumour ASC recruitment, vascularization and tumour growth promotion. We demonstrate that αSMA expression in ASCs is induced by chemokine signalling and mediates the stimulatory effects of ASCs on endothelial cells. Our data suggest that ASC recruitment to tumours, driven by CXCL1 and CXCL8, promotes prostate cancer progression.

Suggested Citation

  • Tao Zhang & Chieh Tseng & Yan Zhang & Olga Sirin & Paul G. Corn & Elsa M. Li-Ning-Tapia & Patricia Troncoso & John Davis & Curtis Pettaway & John Ward & Marsha L. Frazier & Christopher Logothetis & Mi, 2016. "CXCL1 mediates obesity-associated adipose stromal cell trafficking and function in the tumour microenvironment," Nature Communications, Nature, vol. 7(1), pages 1-16, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11674
    DOI: 10.1038/ncomms11674
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