Tumor Acidosis and Hypoxia Differently Modulate the Inflammatory Program: Measurements In Vitro and In Vivo Anne Riemann, Sarah Reime, Oliver Thews

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Tumor Acidosis and Hypoxia Differently Modulate the Inflammatory Program: Measurements In Vitro and In Vivo Anne Riemann, Sarah Reime, Oliver Thews Neoplasia Volume 19, Issue 12, Pages 1033-1042 (December 2017) DOI: 10.1016/j.neo.2017.09.005 Copyright © 2017 The Authors Terms and Conditions

Figure 1 Change in MCP-1, IL-6, and TNF-α expression in AT1 and Walker-256 cells during extracellular acidosis (pH 6.6), hypoxia (pO2=1.5 mmHg), or combined acidosis+hypoxia. n=5-17 for AT1, n=4-11 for Walker-256; *P<.05; n.d., not detectable. Neoplasia 2017 19, 1033-1042DOI: (10.1016/j.neo.2017.09.005) Copyright © 2017 The Authors Terms and Conditions

Figure 2 Changes in iNOS and OPN expression in AT1 and Walker-256 cells during extracellular acidosis (pH 6.6), hypoxia (pO2=1.5 mmHg), or combined acidosis+hypoxia. n=4-17 for AT1, n=5-13 for Walker-256; *P<.05. Neoplasia 2017 19, 1033-1042DOI: (10.1016/j.neo.2017.09.005) Copyright © 2017 The Authors Terms and Conditions

Figure 3 Modulation of the expression of inflammatory mediators in solid (A) AT1 and (B) Walker-256 tumors (black bars) by combined acidosis and hypoxia for 24 hours. For comparison, the in vitro data of the respective tumor cells (dark gray) and normal fibroblasts (NRKF, light gray) after the same incubation conditions are shown. n=5 AT1 tumors, n=6 Walker-256 tumors; *P<.05 versus control. Neoplasia 2017 19, 1033-1042DOI: (10.1016/j.neo.2017.09.005) Copyright © 2017 The Authors Terms and Conditions

Figure 4 Change in ERK1/2 and p38 phosphorylation in AT1, Walker-256, and NRKF cells during extracellular acidosis (pH 6.6), hypoxia (pO2=1.5 mmHg), or combined acidosis+hypoxia. The graphs show the change in the ratio of phosphorylated to total MAPK level, normalized to the control (normoxia, pH 7.4). n=5-11 for AT1, n=5-6 for Walker-256, n=5-8 for NRKF; *P<.05 versus control (normoxia, pH 7.4). Neoplasia 2017 19, 1033-1042DOI: (10.1016/j.neo.2017.09.005) Copyright © 2017 The Authors Terms and Conditions

Figure 5 (A) Change in ERK1/2 and p38 phosphorylation in AT1, Walker-256, and NRKF cells during extracellular acidosis (pH 6.6) for 3 hours; #P<.05 versus pH 7.4. Modulation of (B) MCP-1, (C) IL-6, and (D) iNOS expression in these cells during extracellular acidosis (pH 6.6) for 3 hours (vehicle) and during acidosis as well as incubation with an inhibitor of the ERK1/2 pathway (U0126) or the p38 pathway (SB203580); *P<.05 versus vehicle. n=5-11 for AT1, n=5-6 for Walker-256, n=5-12 for NRKF. Neoplasia 2017 19, 1033-1042DOI: (10.1016/j.neo.2017.09.005) Copyright © 2017 The Authors Terms and Conditions