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

Available from: 2018-01-31 Created: 2018-01-31 Last updated: 2023-03-28Bibliographically approved

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