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This stimulates autotaxin (ATX) secretion from adipocytes, whereas breast cancer cells produce insignificant ATX. Lysophosphatidate produced by ATX promotes inflammatory cytokine secretion in a vicious inflammatory cycle, which increases tumor growth and metastasis and decreases response to chemotherapy. We hypothesized that damage to adipose tissue during radiotherapy for breast cancer should promote lysophosphatidic acid (LPA) signaling and further inflammatory signaling, which could potentially protect cancer cells from subsequent fractions of radiation therapy. To test this hypothesis, we exposed rat and human adipose tissue to radiation doses (0.25\u20135 Gy) that were expected during radiotherapy. This exposure increased mRNA levels for ATX, cyclooxygenase\u20102, IL\u20101\u03b2, IL\u20106, IL\u201010, TNF\u2010\u03b1, and LPA\n                    <jats:sub>1<\/jats:sub>\n                    and LPA\n                    <jats:sub>2<\/jats:sub>\n                    receptors by 1.8\u2010 to 5.1\u2010fold after 4 to 48 h. There were also 1.5\u2010 to 2.5\u2010fold increases in the secretion of ATX and 14 inflammatory mediators after irradiating at 1 Gy. Inhibition of the radiation\u2010induced activation of NF\u2010\u03baB, cyclooxygenase\u20102, poly (ADP\u2010ribose) polymerase\u20101, or ataxia telangiectasia and Rad3\u2010related protein blocked inflammatory responses to \u03b3\u2010radiation. Consequently, collateral damage to adipose tissue during radiotherapy could establish a comprehensive wound\u2010healing response that involves increased signaling by LPA, cyclooxygenase\u20102, and other inflammatory mediators that could decrease the efficacy of further radiotherapy or chemotherapy.\u2014Meng, G., Tang, X., Yang, Z., Benesch, M. G. K., Marshall, A., Murray, D., Hemmings, D. G., Wuest, F., McMullen, T. P. W., Brindley, D. N. Implications for breast cancer treatment from increased autotaxin production in adipose tissue after radiotherapy. FASEB J. 31, 4064\u20134077 (2017).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                    \u2014Meng, Guanmin, Tang, Xiaoyun, Yang, Zelei, Benesch, Matthew G. K., Marshall, Alison, Murray, David, Hemmings, Denise G., Wuest, Frank, McMullen, Todd P. W., Brindley, David N., Implications for breast cancer treatment from increased autotaxin production in adipose tissue after radiotherapy. 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