YKL40/Integrin β4 Axis Induced by the Interaction between Cancer Cells and Tumor-Associated Macrophages Is Involved in the Progression of High-Grade Serous Ovarian Carcinoma

被引：0

作者：

Yamanaka, Keitaro ^{[1
,2
]}

Koma, Yu-ichiro ^{[1
]}

Urakami, Satoshi ^{[1
,3
]}

Takahashi, Ryosuke ^{[2
]}

Nagamata, Satoshi ^{[2
]}

Omori, Masaki ^{[1
,4
]}

Torigoe, Rikuya ^{[1
,5
]}

Yokoo, Hiroki ^{[1
,5
]}

Nakanishi, Takashi ^{[1
,5
]}

Ishihara, Nobuaki ^{[1
,4
]}

Tsukamoto, Shuichi ^{[1
]}

Kodama, Takayuki ^{[1
]}

Nishio, Mari ^{[1
]}

Shigeoka, Manabu ^{[1
]}

Yokozaki, Hiroshi ^{[1
]}

Terai, Yoshito ^{[2
]}

机构：

[1] Kobe Univ, Grad Sch Med, Dept Pathol, Div Pathol, Kobe 6500017, Japan

[2] Kobe Univ, Dept Surg Related, Div Obstet & Gynecol, Grad Sch Med, Kobe 6500017, Japan

[3] Kobe Univ, Grad Sch Med, Dept Internal Med, Div Gastroenterol, Kobe 6500017, Japan

[4] Kobe Univ, Grad Sch Med, Dept Surg, Div Hepatobiliary Pancreat Surg, Kobe 6500017, Japan

[5] Kobe Univ, Dept Surg, Div Gastrointestinal Surg, Grad Sch Med, Kobe 6500017, Japan

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2024年 / 25卷 / 19期

基金：

日本学术振兴会;

关键词：

epithelial ovarian cancer; high-grade serous ovarian carcinoma; tumor-associated macrophages; tumor microenvironment; YKL40; M2-POLARIZED MACROPHAGES; CHITINASE; 3-LIKE-1; PLASMA YKL-40; EXPRESSION; PROGNOSIS; CHEMORESISTANCE; CHEMOTHERAPY; LYMPHOCYTES; MARKER; CHI3L1;

D O I：

10.3390/ijms251910598

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 beta 4, 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 beta 4 correlated with a poor prognosis in patients with serous ovarian carcinoma. Therefore, the YKL40/integrin beta 4 axis may play a role in ovarian cancer progression.

引用

页数：19

共 64 条

[1] Two Closely Related Human Members of Chitinase-like Family, CHI3L1 and CHI3L2, Activate ERK1/2 in 293 and U373 Cells but Have the Different Influence on Cell Proliferation [J].