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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Am+J+Cancer+Res
2015 ; 5
(3
): 1251-64
Nephropedia Template TP
gab.com Text
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English Wikipedia
Contribution of microRNAs in understanding the pancreatic tumor microenvironment
involving cancer associated stellate and fibroblast cells
#MMPMID26046003
Ali S
; Suresh R
; Banerjee S
; Bao B
; Xu Z
; Wilson J
; Philip PA
; Apte M
; Sarkar FH
Am J Cancer Res
2015[]; 5
(3
): 1251-64
PMID26046003
show ga
Understanding of molecular events associated with tumor microenvironment in
pancreatic cancer (PC) is an active area of research especially because of the
rich desmoplasia seen in human PC. Desmoplasia is contributed by several cell
types including cancer-associated fibroblast (CAF) and stellate cells (PSCs),
which are believed to play critical roles in conferring aggressiveness to PC. The
aberrant expression of microRNAs (miRNAs) in PSCs and CAF cells appears to play a
pivotal role in the development and progression of PC. In this study, expression
analysis of miR-21/miR-221 in conditioned media derived from PSCs/CAF cells, and
from PSCs/CAF cells showed up-regulation of both miRNAs compared to MIAPaCa-2 PC
cells. In addition, miR-21 expression in stellate cells derived from normal
pancreas was substantially lower when compared to PSCs or CAF cells. COLO-357 PC
cells cultured in the presence of conditioned media derived from PSC/CAF cells
led to a significant increase in clonogenicity and pancreatosphere formation.
Furthermore, inhibition of miR-21 with antisense oligonucleotide (ASO)
transfection resulted in decreased migration/invasive capacity of PSCs.
Similarly, the effect of ASO-miR-221 transfection in CAF cells reduced the
expression of NF-?B and K-Ras (target of miR-221) along with inhibition of
migration/invasion. Moreover, miRNA expression profiling of PSCs, MIAPaCa-2, and
COLO-357 cells, and further validation by real-time PCR, showed several
differentially expressed miRNAs, among which four was significantly up-regulated.
Collectively, these results suggest a crosstalk between PSCs/CAF cells and PC
cells, resulting in the up-regulation of miR-21/miR-221 expression which in part
may confer aggressiveness to PC. We conclude that targeting these miRNAs could be
useful for developing precision medicine for the prevention of tumor progression
and/or for the treatment of PC.