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Uncarboxylated Osteocalcin Induces Antitumor Immunity against Mouse Melanoma Cell Growth
Yoshikazu Hayashi1,2, Tomoyo Kawakubo-Yasukochi1,3, Akiko Mizokami1,4
1Laboratory of Molecular and Cellular Biochemistry, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, 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.
Insights
Uncarboxylated osteocalcin (GluOC) shows promise as an immunotherapy for melanoma. This study found GluOC suppresses melanoma tumor growth in mice by enhancing T cell responses and inducing cancer cell death.
Area of Science:
- Immunology
- Oncology
- Biochemistry
Background:
- Melanoma treatment faces challenges due to poor response to conventional therapies.
- Novel immune-based therapies involving T cells are needed.
- Osteocalcin, specifically its uncarboxylated form (GluOC), has shown potential in suppressing cancer cell proliferation.
Purpose of the Study:
- To investigate the in vivo anti-melanoma effects of GluOC.
- To elucidate the mechanisms underlying GluOC's action against melanoma.
- To evaluate GluOC's impact on T cell-mediated immunity.
Main Methods:
- Tumor growth suppression was assessed in B16 mouse melanoma models in C57Bl/6N mice.
- In vitro studies examined GluOC's effects on cancer cell proliferation, receptor tyrosine kinase phosphorylation, and apoptosis.
- In vitro T cell proliferation and interferon-γ production were measured using splenocytes stimulated with concanavalin A in the presence of GluOC.
Main Results:
- GluOC significantly suppressed B16 melanoma tumor growth in vivo.
- In vitro, GluOC reduced cancer cell proliferation by downregulating receptor tyrosine kinase phosphorylation and inducing apoptosis.
- GluOC enhanced T cell proliferation and interferon-γ production in stimulated splenocytes.
Conclusions:
- GluOC exhibits in vitro and in vivo anti-melanoma activity.
- GluOC's antitumor effects are mediated through direct cancer cell effects and immunostimulatory actions.
- GluOC represents a potential therapeutic agent for melanoma, leveraging both direct cytotoxicity and immune system activation.
