Protein expression patterns in cancer-associated fibroblasts and cells undergoing the epithelial-mesenchymal transition in ovarian cancers

// Daisuke Fukagawa 1, 2, * , Tamotsu Sugai 1, * , Mitsumasa Osakabe 1 , Yasuko Suga 2 , Takayuki Nagasawa 2 , Hiroaki Itamochi 2 and Toru Sugiyama 2 1 Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, Morioka 020-8505, Japan 2 Department of Obstetrics and Gynecology, School of Medicine, Iwate Medical University, Morioka 020-8505, Japan * These authors have contributed equally to this manuscript Correspondence to: Tamotsu Sugai, email: tsugai@iwate-med.ac.jp Keywords: epithelial-mesenchymal transition; cancer-associated fibroblasts; tumor microenvironment; ovarian cancer Received: March 21, 2018      Accepted: May 14, 2018      Published: June 08, 2018 ABSTRACT Recent studies have shown that cancer-associated fibroblasts (CAFs) and the epithelial-mesenchymal transition (EMT) contribute to invasive and metastatic abilities of ovarian cancer (OC) cells. In the present study, we attempted to identify the role of CAF- and EMT-related proteins in OCs, including serous carcinoma, mucinous carcinoma, endometrioid carcinoma and clear cell carcinoma using an immunohistochemical approach. The following CAF-related markers were used: CD10, podoplanin, fibroblast activating protein (FAP), platelet derived growth factor receptor (PDGFRα), PDGFRβ, S100A4 and α-smooth muscle actin (α-SMA). In addition, the following EMT-related markers were investigated: Slug, TWIST1 and ZEB1We performed hierarchical cluster analysis to group the samples according to their scoring. Subgroup 1 was characterized by high expression of CD10, podoplanin, α-SMA, Slug and ZEB1, whereas subgroup 2 was closely associated with high expression of podoplanin, PDGFRα, PDGFRβ, α-SMA, and Slug. In addition, marked expression of CD10 was observed in subgroup 3. High expression of α-SMA was a distinctive feature in subgroup 4, and expression of podoplanin and α-SMA characterized subgroup 5. Each subgroup was correlated with a histological type. The fact that different histological types were associated with different subgroups suggests the presence of distinct and heterogeneous subpopulations of CAFs in OC.