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.

Details

Title
Stromal and epithelial transcriptional map of initiation progression and metastatic potential of human prostate cancer
Author
Tyekucheva, Svitlana 1 ; Bowden, Michaela 2 ; Bango, Clyde 3 ; Giunchi, Francesca 4 ; Huang, Ying 3 ; Zhou, Chensheng 2   VIAFID ORCID Logo  ; Bondi, Arrigo 5 ; Lis, Rosina 6 ; Mieke Van Hemelrijck 7 ; Andrén, Ove 8 ; Andersson, Sven-Olof 8 ; Watson, R William 9 ; Pennington, Stephen 9 ; Finn, Stephen P 10 ; Martin, Neil E 11 ; Stampfer, Meir J 12 ; Parmigiani, Giovanni 1 ; Penney, Kathryn L 13 ; Fiorentino, Michelangelo 4 ; Mucci, Lorelei A 13 ; Loda, Massimo 14 

 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 
 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA 
 Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA 
 Department of Pathology, Addarii Institute of Oncology, S.Orsola-Malpighi Teaching Hospital, University of Bologna, Bologna, Italy 
 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 
 King’s College London, Division of Cancer Studies, Translational Oncology & Urology Research, Guy’s Hospital, London, UK 
 Department of Urology, 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, Belfield, Dublin, Ireland 
10  Department of Histopathology and Morbid Anatomy, School of Medicine, Trinity College Dublin, Dublin, Ireland 
11  Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA 
12  Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and 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 
13  Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA 
14  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, 415 Main St, Cambridge, MA, USA 
Pages
1-10
Publication year
2017
Publication date
Sep 2017
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
1935293624
Copyright
© 2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.