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

Tyekucheva, Svitlana (author)
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston MA, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston MA, USA
Bowden, Michaela (author)
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston MA, USA
Bango, Clyde (author)
Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston MA, USA
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Giunchi, Francesca (author)
Department of Pathology, Addarii Institute of Oncology, S.Orsola-Malpighi Teaching Hospital, University of Bologna, Bologna, Italy
Huang, Ying (author)
Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston MA, USA
Zhou, Chensheng (author)
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston MA, USA
Bondi, Arrigo (author)
Department of Surgical Pathology, Maggiore Hospital, Bologna, Italy
Lis, Rosina (author)
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston MA, USA; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston MA, USA
Van Hemelrijck, Mieke (author)
Division of Cancer Studies, Translational Oncology, King's College London, London, UK; Urology Research, Guy's Hospital, London, UK
Andrén, Ove, 1963- (author)
Department of Urology, Örebro University Hospital, Örebro, Sweden; School of Health and Medical Sciences, Örebro University Hospital, Örebro, Sweden
Andersson, Sven-Olof, 1949- (author)
Department of Urology, Örebro University Hospital, Örebro, Sweden; School of Health and Medical Sciences, Örebro University Hospital, Örebro, Sweden
Watson, R. William (author)
School of Medicine, UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin (UCD), Dublin, Ireland
Pennington, Stephen (author)
School of Medicine, UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland
Finn, Stephen P. (author)
Department of Histopathology and Morbid Anatomy, School of Medicine, Trinity College Dublin, Dublin, Ireland
Martin, Neil E. (author)
Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston MA, USA
Stampfer, Meir J. (author)
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston MA, USA; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston MA, USA
Parmigiani, Giovanni (author)
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston MA, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston MA, USA
Penney, Kathryn L. (author)
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston MA, USA
Fiorentino, Michelangelo (author)
Department of Pathology, Addarii Institute of Oncology, S.Orsola-Malpighi Teaching Hospital, University of Bologna, Bologna, Italy
Mucci, Lorelei A. (author)
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston MA, USA
Loda, Massimo (author)
Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston MA, USA; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston MA, USA; The Broad Institute, Cambridge MA, USA
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Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston MA, USA; Department of Biostatistics, Harvard TH. Chan School of Public Health, Boston MA, USA Department of Medical Oncology, Dana-Farber Cancer Institute, Boston MA, USA (creator_code:org_t)
2017-09-04
2017
English.
In: Nature Communications. - London, United Kingdom : Nature Publishing Group. - 2041-1723. ; 8:1
Related links:
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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.Stromal cells contribute to tumor development but the mechanisms regulating this process are still unclear. Here the authors analyze gene expression profiles in the prostate and show that stromal gene signature changes ahead of the epithelial gene signature as prostate cancer initiates and progresses.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

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