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Stromal and epithelial transcriptional map of initiation progression and metastatic potential of human prostate cancer

Author

Listed:
  • Svitlana Tyekucheva

    (Dana-Farber Cancer Institute
    Harvard T.H. Chan School of Public Health)

  • Michaela Bowden

    (Dana-Farber Cancer Institute)

  • Clyde Bango

    (Dana-Farber Cancer Institute)

  • Francesca Giunchi

    (University of Bologna)

  • Ying Huang

    (Dana-Farber Cancer Institute)

  • Chensheng Zhou

    (Dana-Farber Cancer Institute)

  • Arrigo Bondi

    (Maggiore Hospital)

  • Rosina Lis

    (Dana-Farber Cancer Institute
    Harvard Medical School)

  • Mieke Van Hemelrijck

    (Translational Oncology & Urology Research, Guy’s Hospital)

  • Ove Andrén

    (Örebro University Hospital)

  • Sven-Olof Andersson

    (Örebro University Hospital)

  • R. William Watson

    (University College Dublin)

  • Stephen Pennington

    (University College Dublin)

  • Stephen P. Finn

    (School of Medicine, Trinity College Dublin)

  • Neil E. Martin

    (Harvard Medical School)

  • Meir J. Stampfer

    (Brigham and Women’s Hospital and Harvard Medical School
    Harvard T.H. Chan School of Public Health
    Harvard T.H. Chan School of Public Health)

  • Giovanni Parmigiani

    (Dana-Farber Cancer Institute
    Harvard T.H. Chan School of Public Health)

  • Kathryn L. Penney

    (Brigham and Women’s Hospital and Harvard Medical School
    Harvard T.H. Chan School of Public Health)

  • Michelangelo Fiorentino

    (University of Bologna)

  • Lorelei A. Mucci

    (Brigham and Women’s Hospital and Harvard Medical School
    Harvard T.H. Chan School of Public Health)

  • Massimo Loda

    (Dana-Farber Cancer Institute
    Harvard Medical School
    The Broad Institute)

Abstract

While progression from normal prostatic epithelium to invasive cancer is driven by molecular alterations, tumor cells and cells in the cancer microenvironment are co-dependent and co-evolve. Few human studies to date have focused on stroma. Here, we performed gene expression profiling of laser capture microdissected normal non-neoplastic prostate epithelial tissue and compared it to non-transformed and neoplastic low-grade and high-grade prostate epithelial tissue from radical prostatectomies, each with its immediately surrounding stroma. Whereas benign epithelium in prostates with and without tumor were similar in gene expression space, stroma away from tumor was significantly different from that in prostates without cancer. A stromal gene signature reflecting bone remodeling and immune-related pathways was upregulated in high compared to low-Gleason grade cases. In validation data, the signature discriminated cases that developed metastasis from those that did not. These data suggest that the microenvironment may influence prostate cancer initiation, maintenance, and metastatic progression.

Suggested Citation

  • Svitlana Tyekucheva & Michaela Bowden & Clyde Bango & Francesca Giunchi & Ying Huang & Chensheng Zhou & Arrigo Bondi & Rosina Lis & Mieke Van Hemelrijck & Ove Andrén & Sven-Olof Andersson & R. William, 2017. "Stromal and epithelial transcriptional map of initiation progression and metastatic potential of human prostate cancer," Nature Communications, Nature, vol. 8(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00460-4
    DOI: 10.1038/s41467-017-00460-4
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    Cited by:

    1. Nader Al-Nakouzi & Chris Kedong Wang & Htoo Zarni Oo & Irina Nelepcu & Nada Lallous & Charlotte B. Spliid & Nastaran Khazamipour & Joey Lo & Sarah Truong & Colin Collins & Desmond Hui & Shaghayegh Esf, 2022. "Reformation of the chondroitin sulfate glycocalyx enables progression of AR-independent prostate cancer," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    2. Hubert Pakula & Mohamed Omar & Ryan Carelli & Filippo Pederzoli & Giuseppe Nicolò Fanelli & Tania Pannellini & Fabio Socciarelli & Lucie Van Emmenis & Silvia Rodrigues & Caroline Fidalgo-Ribeiro & Pie, 2024. "Distinct mesenchymal cell states mediate prostate cancer progression," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    3. Taghreed Hirz & Shenglin Mei & Hirak Sarkar & Youmna Kfoury & Shulin Wu & Bronte M. Verhoeven & Alexander O. Subtelny & Dimitar V. Zlatev & Matthew W. Wszolek & Keyan Salari & Evan Murray & Fei Chen &, 2023. "Dissecting the immune suppressive human prostate tumor microenvironment via integrated single-cell and spatial transcriptomic analyses," Nature Communications, Nature, vol. 14(1), pages 1-20, December.

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