Acidity promotes tumor progression by altering macrophage phenotype in prostate cancer

• DOI: 10.1101/478420
• Publication Date: 2018-11-27T02:15:14Z
• Authors: Asmaa El-Kenawi; Chandler Gatenbee; Mark Robertson-Tessi; Rafael Bravo; Jasreman Dhillon; Yoganand Balaguru...; Anders Berglund; Naveen Visvakarma; Arig Ibrahim-Hashim; Jung Choi; Kimberly Luddy; Robert Gatenby; Shari Pilon-Thomas; Alexander Anderson; Brian Ruffell; Robert Gillies
• Keywords: Tramp; Tumor progression

Tumors rapidly ferment glucose to lactic acid even in the presence of oxygen, and coupling high glycolysis with poor perfusion leads extracellular acidification. Here we demonstrate that acidity, independent from lactate, augments pro-tumor phenotype macrophages. We used zwitterionic buffers show activating macrophages at pH 6.8 vitro enhanced an IL-4-driven as measured by gene expression, cytokine profiling, functional assays. These results were recapitulated vivo wherein neutralizing intratumoral acidity reduced macrophages, while also decreasing tumor incidence invasion TRAMP model prostate cancer. using silico mathematical simulate macrophage responses environmental signals. By turning off acid-induced cellular responses, our modeling shows acid-resistant can limit progression. In summary, this study suggests contributes carcinogenesis altering state activation.