Oncotarget

Research Papers:

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

Bongkun Choi, Eun-Jin Lee, Min-Kyung Shin, Young Soo Park, Min-Hee Ryu, Sang-Min Kim, Eun-Young Kim, Hyung Keun Lee and Eun-Ju Chang _

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Oncotarget. 2016; 7:55506-55517. https://doi.org/10.18632/oncotarget.10747

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Abstract

Bongkun Choi1,5, Eun-Jin Lee1,5, Min-Kyung Shin1,5, Young Soo Park2, Min-Hee Ryu3, Sang-Min Kim1,5, Eun-Young Kim1,5, Hyung Keun Lee4, Eun-Ju Chang1,5

1Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

2Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

3Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

4Department of Ophthalmology and Corneal Dystrophy Research Institute, Yonsei University College of Medicine, Seoul, Korea

5Cell Dysfunction Research Center, University of Ulsan College of Medicine, Seoul, Korea

Correspondence to:

Eun-Ju Chang, email: ejchang@amc.seoul.kr

Keywords: BDNF, PTX3, osteoblast, gastric cancer, bone metastasis

Received: May 04, 2016     Accepted: July 11, 2016     Published: July 21, 2016

ABSTRACT

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.


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