Oxidative stress is exerted by reactive oxygen species (ROS) that accumulate due to an imbalance between ROS generation and elimination, which impacts cellular metabolism and consequently tumorigenesis in the tumor microenvironment. Recently, our group has developed a spinal cord glioma (SCG) model in Göttingen minipigs. However, the mechanism of how SCGs balance redox and thereby modulate cellular proliferation is unclear. Here, we demonstrated that the NRF2/NQO1 signaling, known to mediate oxidative stress, is upregulated in unresectable SCG cells infiltrating at the leading edge compared with the core cells. Moreover, pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6, were significantly elevated in the edge SCG cells. Immunohistochemistry demonstrated positive staining for a higher Ki-67 proliferative index, GFAP, SOX2 and Olig2 in the edge cells compared to the core cells. The oxidative metabolic heterogeneity of immune and stromal cell subtypes among tumor samples was also explored. Hence, our study demonstrated the tumor microenvironment and involvement of the NRF2/NQO1 pathway for redox homeostasis in our minipig SCG model, which can be used to explore targets of the pre-clinical treatment investigations in SCG.

Citation Format: Kecheng Lei, Muhibullah S. Tora, Stewart G. Neill, Purva P. Nagarajan, Thais Federici, Peter Canoll, Nicholas M. Boulis. Oxidative stress triggers tumor edge progression of tumor microenvironment in the minipig spinal cord glioma model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1609.