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RISS 인기검색어
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- 저자 : Brekken, Rolf A. (검색결과 2 건)
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Angiogenic Role of LYVE-1-Positive Macrophages in Adipose Tissue
Cho, Chung-Hyun,Jun Koh, Young,Han, Jinah,Sung, Hoon-Ki,Jong Lee, Hyuek,Morisada, Tohru,Schwendener, Reto A.,Brekken, Rolf A.,Kang, Guson,Oike, Yuichi,Choi, Tae-Saeng,Suda, Toshio,Yoo, Ook-Joon,Koh, G Grune & Stratton 2007 Circulation research Vol.100 No.4
<P>Here we report the discovery of a characteristic dense vascular network (DVN) in the tip portion of epididymal adipose tissue in adult mice. The DVN is formed by angiogenesis rather than by vasculogenesis, and has functional blood circulation. This DVN and its subsequent branching may provide a new functional route for adipogenesis. The recruitment, infiltration, and accumulation of bone marrow-derived LYVE-1(+) macrophages in the tip region are crucial for the formation of the DVN. Matrix metalloproteinases (MMPs) and the VEGF-VEGFR2 system are responsible not only for the formation of the DVN, but also for the recruitment and infiltration of LYVE-1(+) macrophages into the epididymal adipose tissue tip region. SDF-1, but not the MCP-1-CCR2 system, is a critical factor in recruitment and ongoing retention of macrophages in this area. We also demonstrate that the tip region of epididymal adipose tissue is highly hypoxic, and thus provides a microenvironment conducive to the high expression and enhanced activities of VEGF, VEGFR2, MMPs, and SDF-1 in autocrine and paracrine manners, to create an ideal niche for the recruitment, retention, and angiogenic action of macrophages. These findings shed light on the complex interplay between macrophage infiltration, angiogenesis, and adipogenesis in the tip region of adult epididymal adipose tissue, and provide novel insight into the regulation of alternative outgrowth of adipose tissue.</P>
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Jin, Hyejin,Ham, In-Hye,Oh, Hye Jeong,Bae, Cheong A,Lee, Dakeun,Kim, Young-Bae,Son, Sang-Yong,Chwae, Yong-Joon,Han, Sang-Uk,Brekken, Rolf A.,Hur, Hoon American Association for Cancer Research 2018 Molecular Cancer Research Vol.16 No.10
<P>Discoidin domain receptor 1 (DDR1) is activated by fibrillar (triple-helical) collagens and collagen IV, which are major components of tumor stroma; thus, DDR1 might be a critical mediator of communication between cancer cells and stroma. The aim of this study was to investigate the effect of DDR1 inhibition on stroma-induced peritoneal metastasis in gastric carcinoma. We analyzed by immunohistochemistry the correlation between DDR1 expression and the pattern of recurrence in gastric carcinoma tissues from a previously characterized and established gastric carcinoma patient cohort. We also cocultured human gastric carcinoma cell lines with gastric cancer–associated fibroblasts (CAF) and investigated DDR1 expression and activation. We evaluated CAF-induced tumorigenic properties of gastric carcinoma cell lines and the effect of a DDR1-specific inhibitor in organotypic cultures and in a peritoneal seeding xenograft animal model. The expression of DDR1 in gastric cancer tissues was positively associated with early recurrence (<I>P</I> = 0.043) and a high incidence of peritoneal recurrence (<I>P</I> = 0.036). We confirmed that coculturing with CAFs elevated DDR1 protein expression in gastric carcinoma cell lines and enhanced gastric carcinoma cell line spheroid formation in organotypic cultures in a tumor cell DDR1-dependent manner. Coimplantation of CAFs with gastric carcinoma cells enhanced peritoneal tumor formation <I>in vivo</I>, an effect that was sensitive to pharmacologic inhibition of DDR1.</P><P><B>Implications:</B> This study highlights that CAF-induced elevation of DDR1 expression in gastric carcinoma cells enhances peritoneal tumorigenesis, and that inhibition of DDR1 is an attractive strategy for the treatment of gastric carcinoma peritoneal metastasis. <I>Mol Cancer Res; 16(10); 1590–600. ©2018 AACR</I>.</P>
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