Adrenergic Receptor Signaling Regulates the Response of Tumors to Ionizing Radiation.

Adrenergic Receptor Signaling Regulates the Response of Tumors to Ionizing Radiation. Radiat Res. 2019 Apr 25;: Authors: MacDonald CR, Bucsek MJ, Qiao G, Chen M, Evans L, Greenberg DJ, Uccello TP, Battaglia NG, Hylander BL, Singh AK, Lord EM, Gerber SA, Repasky EA Abstract While ionizing radiation is a major form of cancer therapy, radioresistance remains a therapeutic obstacle. We have previously shown that the mandated housing temperature for laboratory mice (∼22°C) induces mild, but chronic, cold stress resulting in increased circulating norepinephrine, which binds to, and triggers activation of, beta-adrenergic receptors (β-AR) on tumor and immune cells. This adrenergic signaling increases tumor cell intrinsic resistance to chemotherapy and suppression of the anti-tumor immune response. These findings led us to hypothesize that adrenergic stress signaling increases radioresistance in tumor cells in addition to suppressing T-cell-mediated anti-tumor immunity, thus suppressing the overall sensitivity of tumors to radiation. We used three strategies to test the effect of adrenergic signaling on responsiveness to radiation. For one strategy, mice implanted with CT26 murine colon adenocarcinoma were housed at either 22°C or at thermoneutrality (30°C), which reduces physiological adrenergic stress. For a second strategy, we used a β-AR antagonist ("beta blocker") to block adrenergic signaling in mice housed at 22°C. In either c...
Source: Radiation Research - Category: Physics Authors: Tags: Radiat Res Source Type: research