Periostin in Cancer-Associated Fibroblasts Promotes Esophageal Squamous Cell Carcinoma Progression by Enhancing Cancer and Stromal Cell Migration

被引：13

作者：

Miyako, Shoji ^{[1
,2
]}

Koma, Yu-ichiro ^{[1
,2
]}

Nakanishi, Takashi ^{[1
]}

Tsukamoto, Shuichi ^{[1
]}

Yamanaka, Keitaro ^{[1
,4
]}

Ishihara, Nobuaki ^{[1
,3
]}

Azumi, Yuki ^{[1
,2
]}

Urakami, Satoshi ^{[1
,5
]}

Shimizu, Masaki ^{[2
]}

Kodama, Takayuki ^{[1
]}

Nishio, Mari ^{[1
]}

Shigeoka, Manabu ^{[1
]}

Kakeji, Yoshihiro ^{[1
,2
]}

Yokozaki, Hiroshi ^{[1
]}

机构：

[1] Kobe Univ, Grad Sch Med, Dept Pathol, Div Pathol, 7-5-1 Kusunoki Cho,Chuo Ku, Kobe 6500017, Japan

[2] Kobe Univ, Grad Sch Med, Div Gastro Intestinal Surg, Kobe, Japan

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

[4] Kobe Univ, Grad Sch Med, Div Obstet & Gynecol, Kobe, Japan

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

来源：

AMERICAN JOURNAL OF PATHOLOGY | 2024年 / 194卷 / 05期

基金：

日本学术振兴会;

关键词：

ANCHORAGE-INDEPENDENT GROWTH; TGFBI EXPRESSION; POOR-PROGNOSIS; IN-VITRO; INVASION; PROLIFERATION; PROTEIN; MICROENVIRONMENT; INVASIVENESS; ANGIOGENESIS;

D O I：

10.1016/j.ajpath.2023.12.010

中图分类号：

R36 [病理学];

学科分类号：

100104 ;

摘要：

Cancer-associated fibroblasts (CAFs) in the tumor microenvironment are involved in the progression of various cancers, including esophageal squamous cell carcinoma (ESCC). CAF-like cells were generated through direct co-culture of human bone marrow-derived mesenchymal stem cells, one of CAF origins, with ESCC cells. Periostin (POSTN) was found to be highly expressed in CAF-like cells. After direct coculture, ESCC cells showed increased malignant phenotypes, such as survival, growth, and migration, as well as increased phosphorylation of Akt and extracellular signal-regulated kinase (Erk). Recombinant human POSTN activated Akt and Erk signaling pathways in ESCC cells, enhancing survival and migration. The suppression of POSTN in CAF-like cells by siRNA during direct co-culture also suppressed enhanced survival and migration in ESCC cells. In ESCC cells, knockdown of POSTN receptor integrin b4 inhibited Akt and Erk phosphorylation, and survival and migration increased by POSTN. POSTN also enhanced mesenchymal stem cell and macrophage migration and endowed macrophages with tumor-associated macrophage-like properties. Immunohistochemistry showed that high POSTN expression in the cancer stroma was significantly associated with tumor invasion depth, lymphatic and blood vessel invasion, higher pathologic stage, CAF marker expression, and infiltrating tumor-associated macrophage numbers. Moreover, patients with ESCC with high POSTN expression exhibited poor postoperative outcomes. Thus, CAF-secreted POSTN contributed to tumor microenvironment development. These results indicate that POSTN may be a novel therapeutic target for ESCC. (Am J Pathol 2024, 194: 828-848; https://doi.org/10.1016/j.ajpath.2023.12.010)

引用

页码：828 / 848

页数：21

共 69 条

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