Upregulation of brain-derived neurotrophic factor in advanced gastric cancer contributes to bone metastatic osteolysis by inducing long pentraxin 3

被引：39

作者：

Choi, Bongkun ^{[1
,6
]}

Lee, Eun-Jin ^{[1
,6
]}

Shin, Min-Kyung ^{[1
,6
]}

Park, Young Soo ^{[2
]}

Ryu, Min-Hee ^{[3
]}

Kim, Sang-Min ^{[1
,6
]}

Kim, Eun-Young ^{[1
,6
]}

Lee, Hyung Keun ^{[4
,5
]}

Chang, Eun-Ju ^{[1
,6
]}

机构：

[1] Univ Ulsan, Dept Biomed Sci, Asan Med Ctr, Coll Med, Seoul, South Korea

[2] Univ Ulsan, Dept Pathol, Asan Med Ctr, Coll Med, Seoul, South Korea

[3] Univ Ulsan, Dept Oncol, Asan Med Ctr, Coll Med, Seoul, South Korea

[4] Yonsei Univ, Coll Med, Dept Ophthalmol, Seoul, South Korea

[5] Yonsei Univ, Coll Med, Corneal Dystrophy Res Inst, Seoul, South Korea

[6] Univ Ulsan, Coll Med, Cell Dysfunct Res Ctr, Seoul, South Korea

来源：

ONCOTARGET | 2016年 / 7卷 / 34期

基金：

新加坡国家研究基金会;

关键词：

BDNF; PTX3; osteoblast; gastric cancer; bone metastasis; STEM-CELL NICHE; KINASE-B; BREAST-CANCER; RECEPTOR TRKB; IN-VITRO; EXPRESSION; CARCINOMA; INFLAMMATION; MARROW; DIFFERENTIATION;

D O I：

10.18632/oncotarget.10747

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The brain-derived neurotrophic factor (BDNF) activates its receptor, tropomyosin receptor kinase B (TrkB; also called NTRK2) that has been shown to promote the malignant progression of several cancers. In this study, we investigated the clinical and biological significance of the BDNF/TrkB axis in the progression of human gastric cancer. The increased co-expression of the BDNF/TrkB axis was significantly correlated with bone metastatic properties in advanced gastric cancers. BDNF acting via TrkB receptors increased the levels of long pentraxin 3 (PTX3) that was related to bone metastatic status of gastric cancer by enhancing gastric cancer-osteoblastic niche interactions. In bone metastatic gastric cancer, PTX3 knockdown using small interfering RNA significantly inhibited BDNF-induced interactions of cancer cells with osteoblasts. Moreover, BDNF-derived PTX3 induction supported subsequent osteoclastogenesis, and this effect was significantly reversed by PTX3 silencing. These findings suggest that a functional interaction between BDNF/TrkB and PTX3 enhances the osteolysis of bone metastatic gastric cancer, thereby providing potential prognostic factors for the development of bone metastasis of gastric cancer.

引用

页码：55506 / 55517

页数：12

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