Metformin Prevents Peritoneal Dissemination via Immune-suppressive Cells in the Tumor Microenvironment

Takanori Hirayama, Yasuhiro Nagata, Mikako Nishida, Mitsutoshi Matsuo, Shinichiro Kobayashi, Akira Yoneda, Kengo Kanetaka, Heiichiro Udono, Susumu Eguchi

Research output: Contribution to journalArticle

Abstract

Background/Aim: Metformin, a drug for type 2 diabetes, also exerts anticancer effects. This study addressed the immunological effects of metformin on peritoneal dissemination. Materials and Methods: We developed a mouse model of peritoneal dissemination via intraperitoneal injection of RLmale1, an X-ray-induced leukemia cell line, into BALB/c mice. Cell-surface markers, cytokine production, and myeloid-derived suppressor cells (MDSCs) were examined in cells from spleen and peritoneal lavage fluid. Results: Metformin-treated mice exhibited suppressed intraperitoneal tumor growth and extended survival, and these effects were lost in mice with severe combined immunodeficiency. MDSCs induction was inhibited in metformin-treated mice. Although MDSC mobilization into the peritoneal cavity was correlated with suppression of interferon-γ production by tumor-infiltrating lymphocytes, the T-helper 1 ability of these lymphocytes was preserved in metformin-treated mice. Conclusion: Our findings demonstrate the action of metformin on both intraperitoneal tumors and immune-suppressive cells and might contribute to the development of immunotherapy against peritoneal dissemination.

Original languageEnglish
Pages (from-to)4699-4709
Number of pages11
JournalAnticancer research
Volume39
Issue number9
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Tumor Microenvironment
Metformin
Peritoneal Lavage
Tumor-Infiltrating Lymphocytes
Severe Combined Immunodeficiency
Ascitic Fluid
Peritoneal Cavity
Intraperitoneal Injections
Immunotherapy
Type 2 Diabetes Mellitus
Interferons
Neoplasms
Leukemia
Spleen
X-Rays
Lymphocytes
Cytokines
Cell Line
Growth
Pharmaceutical Preparations

Keywords

  • Metformin
  • Myeloid derived suppressor cell
  • Peritoneal dissemination
  • Tumor microenvironment

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Hirayama, T., Nagata, Y., Nishida, M., Matsuo, M., Kobayashi, S., Yoneda, A., ... Eguchi, S. (2019). Metformin Prevents Peritoneal Dissemination via Immune-suppressive Cells in the Tumor Microenvironment. Anticancer research, 39(9), 4699-4709. https://doi.org/10.21873/anticanres.13652

Metformin Prevents Peritoneal Dissemination via Immune-suppressive Cells in the Tumor Microenvironment. / Hirayama, Takanori; Nagata, Yasuhiro; Nishida, Mikako; Matsuo, Mitsutoshi; Kobayashi, Shinichiro; Yoneda, Akira; Kanetaka, Kengo; Udono, Heiichiro; Eguchi, Susumu.

In: Anticancer research, Vol. 39, No. 9, 01.01.2019, p. 4699-4709.

Research output: Contribution to journalArticle

Hirayama, T, Nagata, Y, Nishida, M, Matsuo, M, Kobayashi, S, Yoneda, A, Kanetaka, K, Udono, H & Eguchi, S 2019, 'Metformin Prevents Peritoneal Dissemination via Immune-suppressive Cells in the Tumor Microenvironment', Anticancer research, vol. 39, no. 9, pp. 4699-4709. https://doi.org/10.21873/anticanres.13652
Hirayama, Takanori ; Nagata, Yasuhiro ; Nishida, Mikako ; Matsuo, Mitsutoshi ; Kobayashi, Shinichiro ; Yoneda, Akira ; Kanetaka, Kengo ; Udono, Heiichiro ; Eguchi, Susumu. / Metformin Prevents Peritoneal Dissemination via Immune-suppressive Cells in the Tumor Microenvironment. In: Anticancer research. 2019 ; Vol. 39, No. 9. pp. 4699-4709.
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