title: Upregulation of brain-derived neurotrophic factor in advanced gastric cancer contributes to bone metastatic osteolysis by inducing long pentraxin 3.
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.
authors.affiliation: Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.|Cell Dysfunction Research Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Bongkun
authors.initials: B
authors.lastname: Choi
authors.affiliation: Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.|Cell Dysfunction Research Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Eun-Jin
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.|Cell Dysfunction Research Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Min-Kyung
authors.initials: MK
authors.lastname: Shin
authors.affiliation: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Young Soo
authors.initials: YS
authors.lastname: Park
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Min-Hee
authors.initials: MH
authors.lastname: Ryu
authors.affiliation: Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.|Cell Dysfunction Research Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Sang-Min
authors.initials: SM
authors.lastname: Kim
authors.affiliation: Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.|Cell Dysfunction Research Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Kim
authors.affiliation: Department of Ophthalmology and Corneal Dystrophy Research Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hyung Keun
authors.initials: HK
authors.lastname: Lee
authors.affiliation: Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.|Cell Dysfunction Research Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: Eun-Ju
authors.initials: EJ
authors.lastname: Chang
mesh_terms: D001859:Bone Neoplasms / Q000556:secondary*; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology*; D002097:C-Reactive Protein / Q000502:physiology*; D045744:Cell Line, Tumor; D002630:Chemotactic Factors; D006801:Humans; D008562:Membrane Glycoproteins / Q000502:physiology; D010014:Osteolysis; D020813:Receptor, trkB / Q000502:physiology; D000683:Serum Amyloid P-Component / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013274:Stomach Neoplasms / Q000473:pathology*; D015854:Up-Regulation; D000099153:Pentraxins
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D002097:C-Reactive Protein; D002630:Chemotactic Factors; D008562:Membrane Glycoproteins; D020813:Receptor, trkB; D000683:Serum Amyloid P-Component; D000099153:Pentraxins; C579455:BDNF protein, human; C000591259:tropomyosin-related kinase-B, human
keywords: BDNF; PTX3; bone metastasis; gastric cancer; osteoblast