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Cancer Microenvironment
Published in: Cancer Microenvironment 1/2015

01-04-2015 | Original Paper

Stromal Expression of Fibroblast Activation Protein Alpha (FAP) Predicts Platinum Resistance and Shorter Recurrence in patients with Epithelial Ovarian Cancer

Authors: Paulette Mhawech-Fauceglia, Li Yan, Maryam Sharifian, Xing Ren, Song Liu, Grace Kim, Simon A. Gayther, Tanja Pejovic, Kate Lawrenson

Published in: Cancer Microenvironment | Issue 1/2015

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Abstract

The microenvironment plays an important role in tumorigenesis. Fibroblast activation protein alpha (FAP) is overexpressed by fibroblasts present in the microenvironment of many tumors. High FAP expression is a negative prognostic factor in several malignancies, but this has not been investigated in epithelial ovarian cancer (EOC). The aim of this study is to define the value of FAP in EOC. Immunohistochemical staining using an anti-FAP antibody was performed on 338 EOC tissues. mRNA levels in cancer cell lines and FAP silencing using siRNA was also done. FAP immunoexpression by tumor stroma was a significant predictive factor for platinum resistance (p = 0.0154). In survival analysis of days to recurrence, FAP stoma + was associated with shorter recurrence than those with FAP − stroma (p = 0.0247). In 21.8 % of tumors, FAP protein was expressed by the tumor epithelium, and FAP mRNA was more highly expressed in tumors (n = 489) than in normal tissues (n = 8) (p = 3.88 × 10−4). In vitro, addition of FAP to EOC cells induced a 10–12 % increase in cell viability both in the presence and absence of cisplatin. Conversely, siRNA silencing of FAP resulted in ~10 % reduction in EOC cell proliferation. We have shown that FAP expression in EOC is associated with poorer clinical outcomes. FAP may have novel cell-autonomous effects suggesting that targeting FAP could have pleiotropic anti-tumor effects, and anti-FAP therapy could be a highly effective novel treatment for EOC, especially in cisplatinum-resistant cases.
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Metadata
Title
Stromal Expression of Fibroblast Activation Protein Alpha (FAP) Predicts Platinum Resistance and Shorter Recurrence in patients with Epithelial Ovarian Cancer
Authors
Paulette Mhawech-Fauceglia
Li Yan
Maryam Sharifian
Xing Ren
Song Liu
Grace Kim
Simon A. Gayther
Tanja Pejovic
Kate Lawrenson
Publication date
01-04-2015
Publisher
Springer Netherlands
Published in
Cancer Microenvironment / Issue 1/2015
Print ISSN: 1875-2292
Electronic ISSN: 1875-2284
DOI
https://doi.org/10.1007/s12307-014-0153-7

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