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

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 Watson, Stephen Pennington, Stephen P. Finn, Neil E. Martin, Meir J. Stampfer, Giovanni Parmigiani, Kathryn L. Penney, Michelangelo Fiorentino, Lorelei A. Mucci and Massimo Loda ()
Additional contact information
Svitlana Tyekucheva: Dana-Farber Cancer Institute
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
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
Giovanni Parmigiani: Dana-Farber Cancer Institute
Kathryn L. Penney: Brigham and Women’s Hospital and Harvard Medical School
Michelangelo Fiorentino: University of Bologna
Lorelei A. Mucci: Brigham and Women’s Hospital and Harvard Medical School
Massimo Loda: Dana-Farber Cancer Institute

Nature Communications, 2017, vol. 8, issue 1, 1-10

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-00460-4

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