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.