title: Characterization of beta-tricalcium phosphate as a novel immunomodulator.
abstract: Calcium phosphate (CaP) ceramics including hydroxyapatite (HA) and beta-tricalcium phosphate (β-TCP) have been widely used for bone substitution in orthopedic, maxillofacial and dental surgery, as well as in tumor resections. CaP particles are also known to cause inflammatory responses, which are thought to be an unfavorable characteristic of prosthetic coating materials. On the other hand, the immunostimulatory effect of β-TCP induces an anti-tumor effect in xenograft tumor models in athymic mice. To date, in depth analysis of the biological effects of β-TCP has not been studied in mice. In the present study, in vivo biological effects of β-TCP were investigated by subcutaneously injecting β-TCP particles into mice. This induced extensive migration of immune cells to the area surrounding the injection. In addition, we found that in vitro treatment with β-TCP in murine monocyte/macrophage cells (J774A.1) induced up-regulation of surface expression of CD86, and increased production of TNF-α, MIP-1α, and sICAM-1. Furthermore, conditioned medium from J774A.1 cells treated with β-TCP facilitated migration of murine splenocytes in a transwell migration assay. These findings clarify that β-TCP induces an immunostimulatory effect in mice, and suggest a potential for β-TCP as a novel adjuvant for cancer therapy.
authors.affiliation: Experimental Animal Facility, Shizuoka Cancer Center Research Institute, Shizuoka, Japan; Division of Life Sciences, Graduate School of Humanities and Sciences, Ochanomizu University, Tokyo, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Tai
authors.affiliation: Advanced Analysis Technology Department, Corporate R&D Center, Olympus Corporation, Tokyo, Japan.
authors.forename: Jin-Yan
authors.initials: JY
authors.lastname: Cheng
authors.affiliation: Experimental Animal Facility, Shizuoka Cancer Center Research Institute, Shizuoka, Japan.
authors.forename: Hidee
authors.initials: H
authors.lastname: Ishii
authors.affiliation: Department of Pediatric Hematology and Oncology Research, National Medical Center for Children and Mothers Research Institute, Tokyo, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Akimoto
authors.affiliation: Advanced Analysis Technology Department, Corporate R&D Center, Olympus Corporation, Tokyo, Japan.
authors.forename: Takatomo
authors.initials: T
authors.lastname: Satoh
authors.affiliation: Department of Diagnostic Pathology, Shizuoka Cancer Center Hospital, Shizuoka, Japan.
authors.forename: Kazumi
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Department of Diagnostic Pathology, Shizuoka Cancer Center Hospital, Shizuoka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakajima
authors.affiliation: Advanced Analysis Technology Department, Corporate R&D Center, Olympus Corporation, Tokyo, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Karaki
authors.affiliation: Division of Life Sciences, Graduate School of Humanities and Sciences, Ochanomizu University, Tokyo, Japan.
authors.forename: Emiko
authors.initials: E
authors.lastname: Suzuki
authors.affiliation: Shizuoka Cancer Center Hospital and Research Institute, Shizuoka, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Yamaguchi
authors.affiliation: Experimental Animal Facility, Shizuoka Cancer Center Research Institute, Shizuoka, Japan. Electronic address: k.maruyama@scchr.jp.
authors.forename: Kouji
authors.initials: K
authors.lastname: Maruyama
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D051940:B7-2 Antigen / Q000378:metabolism; D002130:Calcium Phosphates / Q000494:pharmacology*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D054405:Chemokine CCL3 / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000187:drug effects / Q000502:physiology; D010587:Phagocytosis / Q000187:drug effects; D013154:Spleen / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D051940:B7-2 Antigen; D002130:Calcium Phosphates; C496534:Ccl3 protein, mouse; C497965:Cd86 protein, mouse; D054405:Chemokine CCL3; C090509:Icam1 protein, mouse; D014409:Tumor Necrosis Factor-alpha; C485817:beta-tricalcium phosphate; D018799:Intercellular Adhesion Molecule-1
keywords: Adjuvant; Beta-tricalcium phosphate; Cancer immunotherapy; In vivo and in vitro immunostimulatory effects