Cyclooxygenase-2 Inhibition Attenuates Hypoxic Cancer Cells Induced M2-Polarization of Macrophages
Corresponding Author(s) : M.L.B. Bhatt
Cellular and Molecular Biology,
Vol. 60 No. 3: Issues 3
Tumor associated macrophages (TAMs), represent a major subpopulation of tumor infiltrating immune cells. These alternatively activated M2-polarized macrophages are well known for their pro-tumor functions. Owing to their established role in potentiating tumor-neovasculogenesis and metastasis, TAMs have emerged as promising target for anti-cancer immunotherapy. One of the key TAMs related phenomenon that is amenable to therapeutic intervention is their phenotype switching into alternatively activated M2-polarized macrophages. Hindering macrophage polarization towards a pro-tumor M2 phenotype, or better still reprogramming the M2 like TAMs towards M1 subtype is being considered a beneficial anti-cancer strategy. Hypoxic tumor milieu has been proposed as one of the most plausible factor governing M2-polarization of macrophages. We recently demonstrated that hypoxic tumor cells imparted a pro-angiogenic M2 skewed phenotype to macrophages. Furthermore, sizeable body of data indicates for participation of cyclooxygenase-2 (COX-2) in macrophage polarization. Concordantly, inhibition of COX-2 is associated with impaired macrophage polarization. Prompted by this in the current study we decided to explore if inhibition of COX-2 activity via chemical inhibitors may prevent hypoxic cancer cell induced M2-polarization of macrophages. We observed that treatment with Flunixin meglumine, an established preferential inhibitor of COX-2 activity markedly inhibited hypoxic cancer cell induced of M2-polarization of macrophages thereby indicating for usage of COX-2 inhibition as possible anti-cancer treatment modality.
M2 Polarization COX-2 Hypoxia Flunixin meglumine Pro-angiogenic.
Dubey, P., Shrivastava, R., Tripathi, C., Jain, N. K., Tewari, B. N., Lone, M.-U.-D., Baghel, K. S., Kumar, V., Misra, S., Bhadauria, S., & Bhatt, M. (2014). Cyclooxygenase-2 Inhibition Attenuates Hypoxic Cancer Cells Induced M2-Polarization of Macrophages. Cellular and Molecular Biology, 60(3), 10–15. Retrieved from https://cellmolbiol.org/index.php/CMB/article/view/521
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