| Autor: |
Yamanaka K; Division of Pathology, Department of Pathology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.; Division of Obstetrics and Gynecology, Department of Surgery Related, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan., Koma YI; Division of Pathology, Department of Pathology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan., Urakami S; Division of Pathology, Department of Pathology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.; Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan., Takahashi R; Division of Obstetrics and Gynecology, Department of Surgery Related, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan., Nagamata S; Division of Obstetrics and Gynecology, Department of Surgery Related, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan., Omori M; Division of Pathology, Department of Pathology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.; Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, 650-0017, Japan., Torigoe R; Division of Pathology, Department of Pathology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.; Division of Gastrointestinal Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, 650-0017, Japan., Yokoo H; Division of Pathology, Department of Pathology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.; Division of Gastrointestinal Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, 650-0017, Japan., Nakanishi T; Division of Pathology, Department of Pathology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.; Division of Gastrointestinal Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, 650-0017, Japan., Ishihara N; Division of Pathology, Department of Pathology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.; Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, 650-0017, Japan., Tsukamoto S; Division of Pathology, Department of Pathology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan., Kodama T; Division of Pathology, Department of Pathology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan., Nishio M; Division of Pathology, Department of Pathology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan., Shigeoka M; Division of Pathology, Department of Pathology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan., Yokozaki H; Division of Pathology, Department of Pathology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan., Terai Y; Division of Obstetrics and Gynecology, Department of Surgery Related, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. |
| Abstrakt: |
Macrophages in the tumor microenvironment, termed tumor-associated macrophages (TAMs), promote the progression of various cancer types. However, many mechanisms related to tumor-stromal interactions in epithelial ovarian cancer (EOC) progression remain unclear. High-grade serous ovarian carcinoma (HGSOC) is the most malignant EOC subtype. Herein, immunohistochemistry was performed on 65 HGSOC tissue samples, revealing that patients with a higher infiltration of CD68 + , CD163 + , and CD204 + macrophages had a poorer prognosis. We subsequently established an indirect co-culture system between macrophages and EOC cells, including HGSOC cells. The co-cultured macrophages showed increased expression of the TAM markers CD163 and CD204, and the co-cultured EOC cells exhibited enhanced proliferation, migration, and invasion. Cytokine array analysis revealed higher YKL40 secretion in the indirect co-culture system. The addition of YKL40 increased proliferation, migration, and invasion via extracellular signal-regulated kinase (Erk) signaling in EOC cells. The knockdown of integrin β4, one of the YKL40 receptors, suppressed YKL40-induced proliferation, migration, and invasion, as well as Erk phosphorylation in some EOC cells. Database analysis showed that high-level expression of YKL40 and integrin β4 correlated with a poor prognosis in patients with serous ovarian carcinoma. Therefore, the YKL40/integrin β4 axis may play a role in ovarian cancer progression. |
