Fig. 7: Naltriben-induced activation of TRPM7 channel promote the M2 phenotype and tumor progression. | npj Precision Oncology

Fig. 7: Naltriben-induced activation of TRPM7 channel promote the M2 phenotype and tumor progression.

From: Naltriben promotes tumor growth by activating the TRPM7-mediated development of the anti-inflammatory M2 phenotype

Fig. 7: Naltriben-induced activation of TRPM7 channel promote the M2 phenotype and tumor progression.

A–C Flow cytometer analysis on M0 activated wild type mice BMDM treated with IL4 or Naltriben-treated cells at different concentrations (20 µM, 30 µM, 50 µM) for 24 hr to show how TRPM7 activation is relevant for macrophage polarization, increasing expression of Arginase 1 (B). Data shown are representative of three independent experiments with similar results. Bar graphs depict average ± SD for relative values, **p ≤ 0.01, (Student’s t-test). C Naïve M0 cells cultured in 6 wells plate (2×106 cells/well) and treated with IL-4 (20 ng/ml) and Naltriben treatment (20 µM, 30 µM and 50 µM) for 24 h. The concentration of anti-inflammatory cytokines (IL-10 and IL-1RA) released in the media was performed by ELISA. Data shown are representative of three independent experiments with similar results. Bar graphs depict average ± SD for relative values, ***p ≤ 0.001 (Student’s t-test). D Elisa quantification for VEGF in supernatants of naïve (M0) BMDM with and without IL-4 treatment (20 ng/ml) and Naltriben treatment (20 µM, 30 µM and 50 µM) for 24 h. Data shown are representative of three independent experiments. Bar graphs depict average ±SD for relative values, **p ≤ 0.01, ***p ≤ 0.001 (Student’s t-test). E Immunoblotting analysis showing the level of expression of arginase and β-actin of wildtype mice naïve M0 with and without IL-4 (20 ng/ml) and Naltriben treatment (20 µM, 30 µM and 50 µM) for 24 h. The data shown are representative of three independent experiments with similar results. F Tumor volumes (average ±SE) under various conditions (n = 6). G The schematic overview of macrophage polarization, where Mg2+ influx drives macrophage phenotype transformation. M1:classically activated and pro-inflammatory cytokines release (IL-6, IL1β, TNFα) is regulated by an uncharacterized Mg2+ influx channel. In contrast activation and anti-inflammatory cytokine release (IL-10, IL-1rn, and IL1RII) are controlled by TRPM7, and it can be induced by Naltriben to promote plasticity.

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