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ITLN1 modulates invasive potential and metabolic reprogramming of ovarian cancer cells in omental microenvironment

Author

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  • Chi-Lam Au-Yeung

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences at Houston)

  • Tsz-Lun Yeung

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences at Houston)

  • Abhinav Achreja

    (University of Michigan)

  • Hongyun Zhao

    (University of Michigan)

  • Kay-Pong Yip

    (University of South Florida)

  • Suet-Ying Kwan

    (The University of Texas MD Anderson Cancer Center)

  • Michaela Onstad

    (The University of Texas MD Anderson Cancer Center)

  • Jianting Sheng

    (Houston Methodist Research Institute, Weill Cornell Medicine
    Center for Precision Oncology, Houston Methodist Cancer Center)

  • Ying Zhu

    (Houston Methodist Research Institute, Weill Cornell Medicine
    Center for Precision Oncology, Houston Methodist Cancer Center)

  • Dodge L. Baluya

    (The University of Texas MD Anderson Cancer Center)

  • Ngai-Na Co

    (The University of Texas MD Anderson Cancer Center)

  • Angela Rynne-Vidal

    (The University of Texas MD Anderson Cancer Center)

  • Rosemarie Schmandt

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences at Houston)

  • Matthew L. Anderson

    (Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine)

  • Karen H. Lu

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences at Houston)

  • Stephen T. C. Wong

    (Houston Methodist Research Institute, Weill Cornell Medicine
    Center for Precision Oncology, Houston Methodist Cancer Center)

  • Deepak Nagrath

    (University of Michigan)

  • Samuel C. Mok

    (The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences at Houston)

Abstract

Advanced ovarian cancer usually spreads to the omentum. However, the omental cell-derived molecular determinants modulating its progression have not been thoroughly characterized. Here, we show that circulating ITLN1 has prognostic significance in patients with advanced ovarian cancer. Further studies demonstrate that ITLN1 suppresses lactotransferrin’s effect on ovarian cancer cell invasion potential and proliferation by decreasing MMP1 expression and inducing a metabolic shift in metastatic ovarian cancer cells. Additionally, ovarian cancer-bearing mice treated with ITLN1 demonstrate marked decrease in tumor growth rates. These data suggest that downregulation of mesothelial cell-derived ITLN1 in the omental tumor microenvironment facilitates ovarian cancer progression.

Suggested Citation

  • Chi-Lam Au-Yeung & Tsz-Lun Yeung & Abhinav Achreja & Hongyun Zhao & Kay-Pong Yip & Suet-Ying Kwan & Michaela Onstad & Jianting Sheng & Ying Zhu & Dodge L. Baluya & Ngai-Na Co & Angela Rynne-Vidal & Ro, 2020. "ITLN1 modulates invasive potential and metabolic reprogramming of ovarian cancer cells in omental microenvironment," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17383-2
    DOI: 10.1038/s41467-020-17383-2
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