Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=26375444
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Integrated gene and miRNA expression analysis of prostate cancer associated
fibroblasts supports a prominent role for interleukin-6 in fibroblast activation
#MMPMID26375444
Doldi V
; Callari M
; Giannoni E
; D'Aiuto F
; Maffezzini M
; Valdagni R
; Chiarugi P
; Gandellini P
; Zaffaroni N
Oncotarget
2015[Oct]; 6
(31
): 31441-60
PMID26375444
show ga
Tumor microenvironment coevolves with and simultaneously sustains cancer
progression. In prostate carcinoma (PCa), cancer associated fibroblasts (CAF)
have been shown to fuel tumor development and metastasis by mutually interacting
with tumor cells. Molecular mechanisms leading to activation of CAFs from
tissue-resident fibroblasts, circulating bone marrow-derived fibroblast
progenitors or mesenchymal stem cells are largely unknown. Through integrated
gene and microRNA expression profiling, we showed that PCa-derived CAF
transcriptome strictly resembles that of normal fibroblasts stimulated in vitro
with interleukin-6 (IL6), thus proving evidence, for the first time, that the
cytokine is able per se to induce most of the transcriptional changes
characteristic of patient-derived CAFs. Comparison with publicly available
datasets, however, suggested that prostate CAFs may be alternatively
characterized by IL6 and TGF?-related signatures, indicating that either signal,
depending on the context, may concur to fibroblast activation. Our analyses also
highlighted novel pathways potentially relevant for induction of a reactive
stroma. In addition, we revealed a role for muscle-specific miR-133b as a soluble
factor secreted by activated fibroblasts to support paracrine activation of
non-activated fibroblasts or promote tumor progression.Overall, we provided
insights into the molecular mechanisms driving fibroblast activation in PCa, thus
contributing to identify novel hits for the development of therapeutic strategies
targeting the crucial interplay between tumor cells and their microenvironment.
free
free
free
