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2017年5月24日，《美国实验生物学会联盟杂志》在线发表加拿大阿尔伯塔大学和中国浙江省立同德医院的研究报告，发现乳腺肿瘤与脂肪组织之间存在炎性相互作用，对机体乳腺脂肪组织进行反复辐射后产生的炎性反应最终可能降低乳腺癌放疗效果。 乳腺癌患者接受乳房肿瘤切除后，需要进行一定剂量的放疗，以确保任何残留乳腺癌细胞被杀灭。放疗期间，患者机体脂肪组织释放自体趋化酶，能够启动伤口愈合反应，阻断防止残留癌细胞的能力，并且促进肿瘤建立自己的领地，以免被破坏。 该研究在放疗期间将大鼠和人类的脂肪组织暴露于一定辐射剂量下，能够导致自体趋化酶水平增加、炎性伤口愈合反应增加。如果使用环氧合酶-2（COX-2）抑制剂之类阻断该炎性反应，即可降低伤口愈合反应，有助于改善放疗效果。 FASEB J. 2017 May 24. [Epub ahead of print] Implications for breast cancer treatment from increased autotaxin production in adipose tissue after radiotherapy. Meng G, Tang X, Yang Z, Benesch MGK, Marshall A, Murray D, Hemmings DG, Wuest F, McMullen TPW, Brindley DN. University of Alberta, Edmonton, Alberta, Canada; Tongde Hospital of Zhejiang Province, Hangzhou, China. We have previously established that adipose tissue adjacent to breast tumors becomes inflamed by tumor-derived cytokines. 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 (0.25-5 Gy) that were expected during radiotherapy. This exposure increased mRNA levels for ATX, cyclooxygenase-2, IL-1β, IL-6, IL-10, TNF-α, and LPA1 and LPA2 receptors by 1.8- to 5.1-fold after 4 to 48 h. There were also 1.5- to 2.5-fold increases in the secretion of ATX and 14 inflammatory mediators after irradiating at 1 Gy. Inhibition of the radiation-induced activation of NF-κB, cyclooxygenase-2, poly (ADP-ribose) polymerase-1, or ataxia telangiectasia and Rad3-related protein blocked inflammatory responses to γ-radiation. Consequently, collateral damage to adipose tissue during radiotherapy could establish a comprehensive wound-healing response that involves increased signaling by LPA, cyclooxygenase-2, and other inflammatory mediators that could decrease the efficacy of further radiotherapy or chemotherapy. KEYWORDS: NF-κB; inflammatory mediators; lysophosphatidate signaling; radioresistance; wound healing PMID: 28539367 PII: fj.201700159R DOI: 10.1096/fj.201700159R
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