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Fibroblast activation protein-α-expressing fibroblasts promote the progression of pancreatic ductal adenocarcinoma

Overview of attention for article published in BMC Gastroenterology, September 2015
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Title
Fibroblast activation protein-α-expressing fibroblasts promote the progression of pancreatic ductal adenocarcinoma
Published in
BMC Gastroenterology, September 2015
DOI 10.1186/s12876-015-0340-0
Pubmed ID
Authors

Tomoya Kawase, Yumiko Yasui, Sohji Nishina, Yuichi Hara, Izumi Yanatori, Yasuyuki Tomiyama, Yoshihiro Nakashima, Koji Yoshida, Fumio Kishi, Masafumi Nakamura, Keisuke Hino

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is characterized by an extensive desmoplastic stromal response. Fibroblast activation protein-α (FAP) is best known for its presence in stromal cancer-associated fibroblasts (CAFs). Our aim was to assess whether FAP expression was associated with the prognosis of patients with PDAC and to investigate how FAP expressing CAFs contribute to the progression of PDAC. FAP expression was immunohistochemically assessed in 48 PDAC specimens. We also generated a fibroblastic cell line stably expressing FAP, and examined the effect of FAP-expressing fibroblasts on invasiveness and the cell cycle in MiaPaCa-2 cells (a pancreatic cancer cell line). Stromal FAP expression was detected in 98 % (47/48) of the specimens of PDAC, with the intensity being weak in 16, moderate in 19, and strong in 12 specimens, but was not detected in the 3 control noncancerous pancreatic specimens. Patients with moderate or strong FAP expression had significantly lower cumulative survival rates than those with negative or weak FAP expression (mean survival time; 352 vs. 497 days, P = 0.006). Multivariate analysis identified moderate to strong expression of FAP as one of the factors associated with the prognosis in patients with PDAC. The intensity of stromal FAP expression was also positively correlated to the histological differentiation of PDAC (P < 0.05). FAP-expressing fibroblasts promoted the invasiveness of MiaPaCa-2 cells more intensively than fibroblasts not expressing FAP. Coculture with FAP-expressing fibroblasts significantly activated cell cycle shift in MiaPaCa-2 cells compared to coculture with fibroblasts not expressing FAP. Furthermore, coculture with FAP expressing fibroblasts inactivated retinoblastoma (Rb) protein, an inhibitor of cell cycle progression, in MiaPaCa-2 cells by promoting phosphorylation of Rb. The present in vitro results and the association of FAP expression with clinical outcomes provide us with a better understanding of the effect of FAP-expressing CAFs on the progression of PDAC.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 90 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 1%
Germany 1 1%
Unknown 88 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 20 22%
Researcher 14 16%
Student > Master 10 11%
Student > Bachelor 8 9%
Other 5 6%
Other 12 13%
Unknown 21 23%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 24 27%
Medicine and Dentistry 16 18%
Agricultural and Biological Sciences 10 11%
Immunology and Microbiology 9 10%
Pharmacology, Toxicology and Pharmaceutical Science 3 3%
Other 6 7%
Unknown 22 24%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 14 May 2016.
All research outputs
#17,772,019
of 22,826,360 outputs
Outputs from BMC Gastroenterology
#1,034
of 1,745 outputs
Outputs of similar age
#180,165
of 267,079 outputs
Outputs of similar age from BMC Gastroenterology
#27
of 49 outputs
Altmetric has tracked 22,826,360 research outputs across all sources so far. This one is in the 19th percentile – i.e., 19% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,745 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.0. This one is in the 35th percentile – i.e., 35% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 267,079 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 27th percentile – i.e., 27% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 49 others from the same source and published within six weeks on either side of this one. This one is in the 30th percentile – i.e., 30% of its contemporaries scored the same or lower than it.