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

Nat Commun
Authors
Keywords
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.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.

Year of Publication
2017
Journal
Nat Commun
Volume
8
Issue
1
Pages
420
Date Published
2017 09 04
ISSN
2041-1723
DOI
10.1038/s41467-017-00460-4
PubMed ID
28871082
PubMed Central ID
PMC5583238
Links
Grant list
P50 CA090381 / CA / NCI NIH HHS / United States
R01 CA187918 / CA / NCI NIH HHS / United States
R21 CA185787 / CA / NCI NIH HHS / United States
R01 CA131945 / CA / NCI NIH HHS / United States
R01 CA174206 / CA / NCI NIH HHS / United States
Wellcome Trust / United Kingdom