Uncarboxylated osteocalcin induces antitumor immunity against mouse melanoma cell growth

Yoshikazu Hayashi, Tomoyo Kawakubo-Yasukochi, Akiko Mizokami, Mai Hazekawa, Tomiko Yakura, Munekazu Naito, Hiroshi Takeuchi, Seiji Nakamura, Masato Hirata

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2478-2486
Number of pages9
JournalJournal of Cancer
Volume8
Issue number13
DOIs
Publication statusPublished - Jan 1 2017

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Osteocalcin
Immunity
Melanoma
Experimental Melanomas
Growth
T-Lymphocytes
Cell Proliferation
Receptor Protein-Tyrosine Kinases
Concanavalin A
Osteoblasts
Mitogens
Interferons
Prostatic Neoplasms
Radiotherapy
Down-Regulation
Phosphorylation
Apoptosis
Transplants
Drug Therapy
Therapeutics

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Hayashi, Y., Kawakubo-Yasukochi, T., Mizokami, A., Hazekawa, M., Yakura, T., Naito, M., ... Hirata, M. (2017). Uncarboxylated osteocalcin induces antitumor immunity against mouse melanoma cell growth. Journal of Cancer, 8(13), 2478-2486. https://doi.org/10.7150/jca.18648

Uncarboxylated osteocalcin induces antitumor immunity against mouse melanoma cell growth. / Hayashi, Yoshikazu; Kawakubo-Yasukochi, Tomoyo; Mizokami, Akiko; Hazekawa, Mai; Yakura, Tomiko; Naito, Munekazu; Takeuchi, Hiroshi; Nakamura, Seiji; Hirata, Masato.

In: Journal of Cancer, Vol. 8, No. 13, 01.01.2017, p. 2478-2486.

Research output: Contribution to journalArticle

Hayashi, Y, Kawakubo-Yasukochi, T, Mizokami, A, Hazekawa, M, Yakura, T, Naito, M, Takeuchi, H, Nakamura, S & Hirata, M 2017, 'Uncarboxylated osteocalcin induces antitumor immunity against mouse melanoma cell growth', Journal of Cancer, vol. 8, no. 13, pp. 2478-2486. https://doi.org/10.7150/jca.18648
Hayashi Y, Kawakubo-Yasukochi T, Mizokami A, Hazekawa M, Yakura T, Naito M et al. Uncarboxylated osteocalcin induces antitumor immunity against mouse melanoma cell growth. Journal of Cancer. 2017 Jan 1;8(13):2478-2486. https://doi.org/10.7150/jca.18648
Hayashi, Yoshikazu ; Kawakubo-Yasukochi, Tomoyo ; Mizokami, Akiko ; Hazekawa, Mai ; Yakura, Tomiko ; Naito, Munekazu ; Takeuchi, Hiroshi ; Nakamura, Seiji ; Hirata, Masato. / Uncarboxylated osteocalcin induces antitumor immunity against mouse melanoma cell growth. In: Journal of Cancer. 2017 ; Vol. 8, No. 13. pp. 2478-2486.
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