High-Fat Diet-Induced Inflammation Accelerates Prostate Cancer Growth via IL6 Signaling
High-Fat Diet-Induced Inflammation Accelerates Prostate Cancer Growth via IL6 Signaling
复制标题
DOI：
10.1158/1078-0432.ccr-18-0106
复制
发表时间：
2018-09-01
影响因子：
11.5
通讯作者：
Nonomura, Norio
中科院分区：
文献类型：
--
作者：
Hayashi, Takuji;Fujita, Kazutoshi;Nonomura, Norio
目的：高脂饮食（HFD）可诱导前列腺癌进展。本研究的目的是确定HFD诱导的前列腺癌进展的机制，重点是inflammation.Experimental设计：我们管理HFD和塞来昔布本地免疫活性Pb-Cre（+）;Pten（fl/fl）模型小鼠前列腺癌。在22周龄时通过肿瘤重量和Ki 67染色评估肿瘤生长，并通过流式细胞术评估局部免疫细胞。鉴定了与肿瘤生长相关的细胞因子，并在小鼠中评价了抑制细胞因子信号后肿瘤生长和局部免疫细胞的变化。结果：HFD可促进肿瘤生长，增加模型小鼠骨髓来源抑制细胞（MDSCs）比例和M2/M1巨噬细胞比例。塞来昔布抑制肿瘤生长，并降低HFD喂养小鼠的局部MDSC和M2/M1巨噬细胞比率。HFD诱导的肿瘤生长与前列腺巨噬细胞分泌的IL 6相关，磷酸化STAT 3（pSTA 13）阳性肿瘤细胞也是如此。在HFD喂养的小鼠中，抗IL 6受体抗体施用抑制肿瘤生长，并降低局部MDSC和pSTAT 3阳性细胞分数。肿瘤浸润的CD 11b阳性细胞计数显着高于在前列腺癌切除术标本的肥胖比那些非肥胖patients with prostate cancer.Conclusions：HFD增加MDSCs和加速前列腺癌肿瘤生长通过IL 6/pSTAT 3信号在小鼠。这种机制可能存在于患有前列腺癌的肥胖患者中。IL 6介导的炎症可能是前列腺癌的治疗靶点。(C)2018年AACR。
Purpose: High-fat diet (HFD) could induce prostate cancer progression. The aim of this study is to identify mechanisms of HFD-induced prostate cancer progression, focusing on inflammation.Experimental Design: We administered HFD and celecoxib to autochthonous immunocompetent Pb-Cre(+) ;Pten(fl/fl) model mice for prostate cancer. Tumor growth was evaluated by tumor weight and Ki67 stain, and local immune cells were assessed by flow cytometry at 22 weeks of age. Cytokines which correlated with tumor growth were identified, and the changes of tumor growth and local immune cells after inhibition of the cytokine signals were evaluated in the mice. IHC analyses using prostatectomy specimens of obese patients were performed.Results: HFD accelerated tumor growth and increased the myeloid-derived suppressor cells (MDSCs) fraction and M2/M1 macrophage ratio in the model mice. Celecoxib-suppressed tumor growth, and decreased both local MDSCs and M2/M1 macrophage ratio in HFD-fed mice. HFD-induced tumor growth was associated with IL6 secreted by prostatic macrophages, as were phosphorylated STAT3 (pSTA13)-positive tumor cells. Anti-IL6 receptor antibody administration suppressed tumor growth, and decreased local MDSCs and pSTAT3-positive cell fractions in HFD-fed mice. The tumor-infiltrating CD11b-positive cell count was significantly higher in prostatectomy specimens of obese than those of nonobese patients with prostate cancer.Conclusions: HFD increased MDSCs and accelerated prostate cancer tumor growth via IL6/pSTAT3 signaling in the mice. This mechanism could exist in obese patients with prostate cancer. IL6-mediated inflammation could be a therapeutic target for prostate cancer. (C) 2018 AACR.