Macrophages, IL-10, and nitric oxide increase, induced by hyperglycemic conditions, impact the development of murine melanoma B16F10-Nex2

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Sellani, Tarciso A. ; Tomaz, Samanta L. ; Goncalves, Jessica M. ; Lima, Adriana ; Herbozo, Carolina C. de Amat ; Silva, Gabrielli N. ; Gambero, Monica ; Longo-Maugeri, Ieda M. ; Simon, Karin A. ; Monteiro, Hugo P. ; Rodrigues, Elaine G.

• Document type: Journal article
• Source: NITRIC OXIDE-BIOLOGY AND CHEMISTRY; v. 148, p. 12-pg., 2024-04-22.

Abstract

Epidemiological studies show a strong correlation between diabetes and the increased risk of developing different cancers, including melanoma. In the present study, we investigated the impact of a streptozotocin (STZ)-induced hyperglycemic environment on B16F10-Nex2 murine melanoma development. Hyperglycemic male C57Bl/6 mice showed increased subcutaneous tumor development, partially inhibited by metformin. Tumors showed increased infiltrating macrophages, and augmented IL-10 and nitric oxide (NO) concentrations. In vivo neutralization of IL-10, NO synthase inhibition, and depletion of macrophages reduced tumor development. STZ-treated TLR4 KO animals showed delayed tumor development; the transfer of hyperglycemic C57Bl/6 macrophages to TLR4 KO reversed this effect. Increased concentrations of IL-10 present in tumor homogenates of hyperglycemic mice induced a higher number of pre-angiogenic structures in vitro, and B16F10-Nex2 cells incubated with different glucose concentrations in vitro produced increased levels of IL-10. In summary, our findings show that a hyperglycemic environment stimulates murine melanoma B16F10-Nex2 primary tumor growth, and this effect is dependent on tumor cell stimulation, increased numbers of macrophages, and augmented IL-10 and NO concentrations. These findings show the involvement of tumor cells and other components of the tumor microenvironment in the development of subcutaneous melanoma under hyperglycemic conditions, defining novel targets for melanoma control in diabetic patients. (AU)

• FAPESP's process: 18/15038-7 - Tumor development under the perspective of redox signaling: temporal modulation of the production of nitric oxide and reactive oxygen species
• Grantee: Hugo Pequeno Monteiro
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 16/06539-7 - INFLAMMATORY AND NITROSATIVE STRESS EVALUATION DURING TUMOR DEVELOPMENT IN HYPERGLICEMIC ENVIRONMENT
• Grantee: Elaine Guadelupe Rodrigues
• Support Opportunities: Regular Research Grants