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Temporal profiling of the breast tumour microenvironment reveals collagen XII as a driver of metastasis

Author

Listed:
  • Michael Papanicolaou

    (The Garvan Institute of Medical Research and The Kinghorn Cancer Centre
    University of Technology Sydney
    Garvan Institute of Medical Research)

  • Amelia L. Parker

    (The Garvan Institute of Medical Research and The Kinghorn Cancer Centre
    Garvan Institute of Medical Research
    UNSW Sydney)

  • Michelle Yam

    (The Garvan Institute of Medical Research and The Kinghorn Cancer Centre
    Garvan Institute of Medical Research)

  • Elysse C. Filipe

    (The Garvan Institute of Medical Research and The Kinghorn Cancer Centre
    Garvan Institute of Medical Research
    UNSW Sydney)

  • Sunny Z. Wu

    (The Garvan Institute of Medical Research and The Kinghorn Cancer Centre
    Garvan Institute of Medical Research
    UNSW Sydney)

  • Jessica L. Chitty

    (The Garvan Institute of Medical Research and The Kinghorn Cancer Centre
    Garvan Institute of Medical Research
    UNSW Sydney)

  • Kaitlin Wyllie

    (The Garvan Institute of Medical Research and The Kinghorn Cancer Centre
    Garvan Institute of Medical Research)

  • Emmi Tran

    (The Garvan Institute of Medical Research and The Kinghorn Cancer Centre
    Garvan Institute of Medical Research)

  • Ellie Mok

    (The Garvan Institute of Medical Research and The Kinghorn Cancer Centre
    Garvan Institute of Medical Research)

  • Audrey Nadalini

    (The Garvan Institute of Medical Research and The Kinghorn Cancer Centre
    Garvan Institute of Medical Research)

  • Joanna N. Skhinas

    (The Garvan Institute of Medical Research and The Kinghorn Cancer Centre
    Garvan Institute of Medical Research)

  • Morghan C. Lucas

    (The Garvan Institute of Medical Research and The Kinghorn Cancer Centre)

  • David Herrmann

    (The Garvan Institute of Medical Research and The Kinghorn Cancer Centre
    Garvan Institute of Medical Research
    UNSW Sydney)

  • Max Nobis

    (The Garvan Institute of Medical Research and The Kinghorn Cancer Centre
    Garvan Institute of Medical Research
    UNSW Sydney)

  • Brooke A. Pereira

    (The Garvan Institute of Medical Research and The Kinghorn Cancer Centre
    Garvan Institute of Medical Research
    UNSW Sydney)

  • Andrew M. K. Law

    (The Garvan Institute of Medical Research and The Kinghorn Cancer Centre)

  • Lesley Castillo

    (The Garvan Institute of Medical Research and The Kinghorn Cancer Centre)

  • Kendelle J. Murphy

    (The Garvan Institute of Medical Research and The Kinghorn Cancer Centre
    Garvan Institute of Medical Research
    UNSW Sydney)

  • Anaiis Zaratzian

    (The Garvan Institute of Medical Research and The Kinghorn Cancer Centre)

  • Jordan F. Hastings

    (The Garvan Institute of Medical Research and The Kinghorn Cancer Centre)

  • David R. Croucher

    (The Garvan Institute of Medical Research and The Kinghorn Cancer Centre
    UNSW Sydney)

  • Elgene Lim

    (The Garvan Institute of Medical Research and The Kinghorn Cancer Centre
    UNSW Sydney)

  • Brian G. Oliver

    (University of Technology Sydney
    The University of Sydney)

  • Fatima Valdes Mora

    (Children’s Cancer Institute
    UNSW Sydney)

  • Benjamin L. Parker

    (University of Sydney)

  • David Gallego-Ortega

    (The Garvan Institute of Medical Research and The Kinghorn Cancer Centre
    UNSW Sydney
    University of Technology Sydney)

  • Alexander Swarbrick

    (The Garvan Institute of Medical Research and The Kinghorn Cancer Centre
    Garvan Institute of Medical Research
    UNSW Sydney)

  • Sandra O’Toole

    (The Garvan Institute of Medical Research and The Kinghorn Cancer Centre
    UNSW Sydney
    Royal Prince Alfred Hospital and NSW Health Pathology)

  • Paul Timpson

    (The Garvan Institute of Medical Research and The Kinghorn Cancer Centre
    Garvan Institute of Medical Research
    UNSW Sydney)

  • Thomas R. Cox

    (The Garvan Institute of Medical Research and The Kinghorn Cancer Centre
    Garvan Institute of Medical Research
    UNSW Sydney)

Abstract

The tumour stroma, and in particular the extracellular matrix (ECM), is a salient feature of solid tumours that plays a crucial role in shaping their progression. Many desmoplastic tumours including breast cancer involve the significant accumulation of type I collagen. However, recently it has become clear that the precise distribution and organisation of matrix molecules such as collagen I is equally as important in the tumour as their abundance. Cancer-associated fibroblasts (CAFs) coexist within breast cancer tissues and play both pro- and anti-tumourigenic roles through remodelling the ECM. Here, using temporal proteomic profiling of decellularized tumours, we interrogate the evolving matrisome during breast cancer progression. We identify 4 key matrisomal clusters, and pinpoint collagen type XII as a critical component that regulates collagen type I organisation. Through combining our proteomics with single-cell transcriptomics, and genetic manipulation models, we show how CAF-secreted collagen XII alters collagen I organisation to create a pro-invasive microenvironment supporting metastatic dissemination. Finally, we show in patient cohorts that collagen XII may represent an indicator of breast cancer patients at high risk of metastatic relapse.

Suggested Citation

  • Michael Papanicolaou & Amelia L. Parker & Michelle Yam & Elysse C. Filipe & Sunny Z. Wu & Jessica L. Chitty & Kaitlin Wyllie & Emmi Tran & Ellie Mok & Audrey Nadalini & Joanna N. Skhinas & Morghan C. , 2022. "Temporal profiling of the breast tumour microenvironment reveals collagen XII as a driver of metastasis," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32255-7
    DOI: 10.1038/s41467-022-32255-7
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    References listed on IDEAS

    as
    1. Claire Vennin & Pauline Mélénec & Romain Rouet & Max Nobis & Aurélie S. Cazet & Kendelle J. Murphy & David Herrmann & Daniel A. Reed & Morghan C. Lucas & Sean C. Warren & Zehra Elgundi & Mark Pinese &, 2019. "CAF hierarchy driven by pancreatic cancer cell p53-status creates a pro-metastatic and chemoresistant environment via perlecan," Nature Communications, Nature, vol. 10(1), pages 1-22, December.
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