Stromal and epithelial transcriptional map of initiation progression and metastatic potential of human prostate cancerDepartment of Oncologic Pathology, Dana-Farber Cancer Institute, Boston MA, USA.
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston MA, USA.
Department of Surgical Pathology, Maggiore Hospital, Bologna, Italy.
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.
Division of Cancer Studies, Translational Oncology, King's College London, London, UK; Urology Research, Guy's Hospital, London, UK.
Department of Urology, Örebro University Hospital, Örebro, Sweden; School of Health and Medical Sciences, Örebro University Hospital, Örebro, Sweden.
Department of Urology, Örebro University Hospital, Örebro, Sweden; School of Health and Medical Sciences, Örebro University Hospital, Örebro, Sweden.
School of Medicine, UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin (UCD), Dublin, Ireland.
School of Medicine, UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland.
Department of Histopathology and Morbid Anatomy, School of Medicine, Trinity College Dublin, Dublin, Ireland.
Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston MA, USA.
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.
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.
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 Pathology, Addarii Institute of Oncology, S.Orsola-Malpighi Teaching Hospital, University of Bologna, Bologna, Italy.
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 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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2017 (English)In: Nature Communications, E-ISSN 2041-1723, Vol. 8, no 1, article id 420Article in journal (Refereed) Published
Abstract [en]
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.
Place, publisher, year, edition, pages
London, United Kingdom: Nature Publishing Group, 2017. Vol. 8, no 1, article id 420
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:oru:diva-64722DOI: 10.1038/s41467-017-00460-4ISI: 000409394000003PubMedID: 28871082Scopus ID: 2-s2.0-85028748686OAI: oai:DiVA.org:oru-64722DiVA, id: diva2:1179049
Funder
NIH (National Institute of Health), RO1CA131945, R01CA187918, DoD PC130716, P50 CA90381
Note
Funding Agencies:
Challenge award from the Prostate Cancer Foundation
Prostate Cancer Foundation
Irish Cancer Society
Wellcome Trust-Health Research Board Dublin Centre for Clinical Research
2018-01-312018-01-312023-03-28Bibliographically approved