演題抄録

FACO International Workshop

開催概要
開催回
第53回・2015年・京都
 

DDR2-collagen axis promote peritoneal dissemination in gastric cancer

演題番号 : FWS8-3

[筆頭演者]
Kurashige Junji:1 
[共同演者]
Iwatsuki Masaaki:1、Kuroda Daisuke:1、Kiyozumi Yuki:1、Kosumi Keisuke:1、Izumi Daisuke:1、Harada Kazuto:1、Tokunaga Ryuma:1、Shigaki Hironobu:1、Sakamoto Yoshio:1、Miyamoto Yuji:1、Baba Yoshifumi:1、Yoshida Naoya:1、Mimori Koshi:2、Baba Hideo:1

1:Department of Gastroenterological Surgery, Graduate School, Kumamoto University、2:Department of Surgery, Beppu Hospital, Kyushu Univercity

 

Background and Objective: Peritoneal dissemination is the most frequent incurable metastasis in patients with advanced gastric cancer, the mechanisms underlying gastric cancer undergoes peritoneal carcinomatosis has not yet been specified. Among the genes contained in the expression signature, we found that discoidin domain receptor 2 (DDR2), a collagen receptor overexpressed in peritoneal disseminated gastric cancer. This observation suggested the importance of the tumor microenvironment niche and Extracellular matrix (ECM) in the gastric peritoneal dissemination. Here, we aimed to clarify the DDR2-collagen axis have a role of promoting the peritoneal dissemination in gastric cancer.
Experimental design: We performed a combined expression analysis of in vivo selected metastatic cell lines and GC patients to identify driver genes for peritoneal dissemination. Furthermore, we compared the clinicopathological significance with between hematogenous and peritoneal disseminated recurrence and we examined collagen expressions used by Sirius Red Stain.
Results: From the genes contained in the expression signature, we found that DDR2 was upregulated by the loss of DNA methylation, and that the knockdown of DDR2 reduced peritoneal metastasis in a xenograft model. Moreover, in clinicopathologic analysis of recurrence patients, peritoneal disseminated recurrence group (n=47) showed higher cancer undifferentiation, more Borrman 3, 4 type, and scirrhous type cancer, Infiltrative growth (INF) c type cancer than hematogenous recurrence group (p<0.05). Furthermore, the peritoneal disseminated recurrence group had a significantly higher collagen expression than the hematogenous recurrence group in gastric cancer stromal (p<0.05).
Conclusions: Our findings suggest that the high expression of collagen in cancer stromal and DDR2 in cancer cells played the important roles of peritoneal dissemination in gastric cancer.

キーワード

臓器別:胃・十二指腸

手法別:トランスレーショナルリサーチ

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