J Cancer 2017; 8(13):2478-2486. doi:10.7150/jca.18648

Research Paper

Uncarboxylated Osteocalcin Induces Antitumor Immunity against Mouse Melanoma Cell Growth

Yoshikazu Hayashi1, 2, Tomoyo Kawakubo-Yasukochi1, 3✉, Akiko Mizokami1, 4, Mai Hazekawa3, Tomiko Yakura5, Munekazu Naito5, Hiroshi Takeuchi6, Seiji Nakamura2, Masato Hirata1, 7✉

1. Laboratory of Molecular and Cellular Biochemistry, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan;
2. Section of Oral and Maxillofacial Oncology, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan;
3. Department of Immunological and Molecular Pharmacology, Faculty of Pharmaceutical Science, Fukuoka University, Fukuoka 814-0180, Japan;
4. OBT Research Center, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan;
5. Department of Anatomy, Aichi Medical University, Aichi 480-1195, Japan;
6. Division of Applied Pharmacology, Kyushu Dental University, Kitakyushu 803-8580, Japan;
7. Fukuoka Dental College, Fukuoka 814-0193, Japan.

Abstract

Because of the poor response to chemotherapy and radiation therapy, new treatment approaches by immune-based therapy involving activated T cells are required for melanoma. We previously reported that the uncarboxylated form of osteocalcin (GluOC), derived from osteoblasts, potentially suppresses human prostate cancer cell proliferation by direct suppression of cell growth. However, the mechanisms in vivo have not been elucidated. In this study, we found that GluOC suppressed tumor growth of B16 mouse melanoma transplants in C57Bl/6N wild-type mice. Our data demonstrated that GluOC suppressed cell growth by downregulating phosphorylation levels of receptor tyrosine kinases and inducing apoptosis in vitro. Additionally, stimulation of primary mouse splenocytes with concanavalin A, a polyclonal T-cell mitogen, in the presence of GluOC increased T cell proliferation and their interferon-γ production. Taken together, we demonstrate that GluOC exerts multiple antitumor effects not only in vitro, but also in vivo through cellular immunostimulatory effects against B16 mouse melanoma cells.

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How to cite this article:
Hayashi Y, Kawakubo-Yasukochi T, Mizokami A, Hazekawa M, Yakura T, Naito M, Takeuchi H, Nakamura S, Hirata M. Uncarboxylated Osteocalcin Induces Antitumor Immunity against Mouse Melanoma Cell Growth. J Cancer 2017; 8(13):2478-2486. doi:10.7150/jca.18648. Available from http://www.jcancer.org/v08p2478.htm