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Vasoactive intestinal peptide blockade suppresses tumor growth by regulating macrophage polarization and function in CT26 tumor-bearing mice.
Kittikulsuth, Wararat; Nakano, Daisuke; Kitada, Kento; Uyama, Toru; Ueda, Natsuo; Asano, Eisuke; Okano, Keiichi; Matsuda, Yoko; Nishiyama, Akira.
Afiliación
  • Kittikulsuth W; Department of Pharmacology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa, 761-0793, Japan. wararat.kittikulsuth@kagawa-u.ac.jp.
  • Nakano D; Department of Pharmacology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa, 761-0793, Japan.
  • Kitada K; Department of Pharmacology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa, 761-0793, Japan.
  • Uyama T; Department of Biochemistry, Faculty of Medicine, Kagawa University, Kagawa, Japan.
  • Ueda N; Department of Biochemistry, Faculty of Medicine, Kagawa University, Kagawa, Japan.
  • Asano E; Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan.
  • Okano K; Department of Gastroenterological Surgery, Faculty of Medicine, Kagawa University, Kagawa, Japan.
  • Matsuda Y; Oncology Pathology, Department of Pathology and Host-Defense, Faculty of Medicine, Kagawa University, Kagawa, Japan.
  • Nishiyama A; Department of Pharmacology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kita, Kagawa, 761-0793, Japan.
Sci Rep ; 13(1): 927, 2023 01 17.
Article en En | MEDLINE | ID: mdl-36650220
Macrophages are a major population of immune cells in solid cancers, especially colorectal cancers. Tumor-associated macrophages (TAMs) are commonly divided into M1-like (tumor suppression) and M2-like (tumor promotion) phenotypes. Vasoactive intestinal peptide (VIP) is an immunoregulatory neuropeptide with a potent anti-inflammatory function. Inhibition of VIP signaling has been shown to increase CD8+ T cell proliferation and function in viral infection and lymphoma. However, the role of VIP in macrophage polarization and function in solid tumors remains unknown. Here, we demonstrated that conditioned medium from CT26 (CT26-CM) cells enhanced M2-related marker and VIP receptor (VPAC) gene expression in RAW264.7 macrophages. VIP hybrid, a VIP antagonist, enhanced M1-related genes but reduced Mrc1 gene expression and increased phagocytic ability in CT26-CM-treated RAW264.7 cells. In immunodeficient SCID mice, VIP antagonist alone or in combination with anti-PD-1 antibody attenuated CT26 tumor growth compared with the control. Analysis of tumor-infiltrating leukocytes found that VIP antagonist increased M1/M2 ratios and macrophage phagocytosis of CT26-GFP cells. Furthermore, Vipr2 gene silencing or VPAC2 activation affected the polarization of CT26-CM-treated RAW264.7 cells. In conclusion, the inhibition of VIP signaling enhanced M1 macrophage polarization and macrophage phagocytic function, resulting in tumor regression in a CT26 colon cancer model.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptido Intestinal Vasoactivo / Neoplasias del Colon / Macrófagos Límite: Animals Idioma: En Revista: Sci Rep Año: 2023 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptido Intestinal Vasoactivo / Neoplasias del Colon / Macrófagos Límite: Animals Idioma: En Revista: Sci Rep Año: 2023 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido