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Macrophage inhibitory cytokine-1 induced by a high-fat diet promotes prostate cancer progression by stimulating tumor-promoting cytokine production from tumor stromal cells

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Cancer Communications 2021年第5期41卷 389-403页

作者： Mingguo Huang Shintaro Narita Atsushi Koizumi taketoshi nara Kazuyuki Numakura Shigeru Satoh Hiroshi Nanjo Tomonori Habuchi Department of Urology Akita University Graduate School of Medicine1-1-1 HondoAkita 010-8543Japan Department of Clinical Pathology Akita University Graduate School of Medicine1-1-1 HondoAkita 010-8543Japan

Background:Recent studies have indicated that a high-fat diet(HFD)and/or HFD-induced obesity may influence prostate cancer(PCa)progression,but the role of HFD in PCa microenvironment is *** study aimed to delineate the molecular mechanisms of PCa progression underHFDmilieus and define the stromal microenvironment focusing on macrophage inhibitory cytokine-1(MIC-1)***:We investigated the effects of HFD on PCa stromal microenvironment and MIC-1 signaling activation using PC-3M-luc-C6 PCa model mice fed with HFD or control ***,we explored the effect of periprostatic adipocytes derived from primary PCa patients on activation and cytokine secretion of prostate stromal *** patterns and roles of MIC-1 signaling on human PCa stroma activation and progression were also ***:HFD stimulated PCa cell growth and invasion as a result of upregulated MIC-1 signaling and subsequently increased the secretion of interleukin(IL)-8 and IL-6 from prostate stromal fibroblasts in PC-3M-luc-C6 PCa *** addition,periprostatic adipocytes directly stimulatedMIC-1 production from PC-3 cells and IL-8 secretion in prostate stromal fibroblasts through the upregulation of adipose lipolysis and free fatty acid *** increased serum MIC-1 was significantly correlated with human PCa stroma activation,high serum IL-8,IL-6,and lipase activity,advanced PCa progression,and high body mass index of the ***-derived neurotrophic factor receptor α-like(GFRAL),a specific receptor of MIC-1,was highly expressed in both cytoplasm and membrane of PCa cells and surrounding stromal fibroblasts,and the expression levelwas decreased by androgen deprivation therapy and ***:HFD-mediated activation of the PCa stromal microenvironment through metabolically upregulated MIC-1 signaling by increased available free fatty acids may be a critical mechanism of HFD and/or obesity-induced PCa progression.

关键词： macrophage inhibitory cytokine-1 tumor microenvironment high-fat diet prostate cancer metabolism

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高脂饮食诱导的巨噬细胞抑制因子-1通过激活肿瘤间质细胞产生促肿瘤细胞因子促进前列腺癌的进展

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癌症 2022年第2期41卷 65-79页

背景与目的最近研究表明高脂饮食(high-fat diet,HFD)和/或HFD诱导的肥胖可影响前列腺癌(prostate cancer,PCa)的进展,但HFD在PCa微环境中的作用尚不清楚。本研究旨在阐明HFD环境下PCa进展的分子机制,描述以巨噬细胞抑制因子-1(macroph... 详细信息

背景与目的最近研究表明高脂饮食(high-fat diet,HFD)和/或HFD诱导的肥胖可影响前列腺癌(prostate cancer,PCa)的进展,但HFD在PCa微环境中的作用尚不清楚。本研究旨在阐明HFD环境下PCa进展的分子机制,描述以巨噬细胞抑制因子-1(macrophage inhibitory cytokine-1,MIC-1)活性为主的肿瘤间质微环境的特征。方法我们利用HFD或正常饮食的PC-3M-luc-C6 PCa小鼠模型,研究了HFD对PCa间质微环境和MIC-1信号活性的影响。我们分离了原发PCa患者来源的前列腺周围脂肪细胞,并研究了其对前列腺间质成纤维细胞活性及其分泌细胞因子的影响。进一步研究了MIC-1信号的表达模式及其对人PCa间质活性和肿瘤进展的影响。结果在PC-3M-luc-C6 PCa小鼠模型中,HFD通过上调前列腺间质成纤维的MIC-1信号通路活性,增加了白介素(interleukin,IL)-8和IL-6的分泌,促进了PCa细胞的生长和侵袭。另外,前列腺周围脂肪细胞通过增加脂肪分解和游离脂肪酸的释放,直接促进了PC-3细胞产生MIC-1和前列腺间质成纤维细胞分泌IL-8。前列腺癌患者血清MIC-1水平增高与人PCa间质活性、高血清IL-8、IL-6水平、脂肪酶高活性、PCa患者疾病进展及高体重指数具有显著相关性。胶质细胞源性神经营养因子受体α(glial-derived neurotrophic factor receptor α-like,GFL)是MIC-1的特异性受体,在PCa细胞和癌周间质成纤维细胞中都出现高表达,雄激素去势治疗和化疗都降低了其表达水平。结论 HFD通过增加游离脂肪酸水平,在代谢水平上调了MIC-1信号活性,从而激活了PCa间质微环境,这可能是HFD和/或脂肪诱导的PCa进展的关键机制。

关键词：巨噬细胞抑制因子-1 肿瘤微环境高脂饮食前列腺癌代谢

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Identification of interleukin-6 (IL-6) and squamous cell carcinoma (SCC) as amniotic fluid-specific markers

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Open Journal of Obstetrics and Gynecology 2012年第2期2卷 147-150页

作者： Katsuhiko Naruse taketoshi Noguchi Shozo Yoshida Taihei Tsunemi Hiroshi Shigetomi Hidekazu Oi Hiroshi Kobayashi Department of Obstetrics and Gynecology Nara Medical University Nara Japan

Objective: To determine if an amniotic fluid (AF)-specific marker is present and if its concentration changes with the presence of labor. Study Design: Twenty-six healthy women who gave birth to healthy newborns at term during the period from July 2009 to January 2010 were included in the study. Six candidate markers were assessed by commercially available ELISA kits: interleukin (IL)-6, squamous cell carcinoma (SCC) antigen, insulin-like growth factor (IGFBP)-1, osteopontin (OPN), CA125, and sialyl Tn (STN). Results: The AF/maternal serum (MS) measurement based on IL-6 or SCC has proved to be superior to IGFBP-1, CA125, OPN and STN. Women with spontaneous labor at term had significantly higher IL-6 and IGFBP-1 concentrations in AF compared with those without labor. No significant differences were observed in the AF concentrations of SCC, OPN, CA125 and STN between women with labor and those not in labor. Conclusion: Our observation of IL-6 and SCC in AF may open a new area of research to assess their usefulness as biological markers of obstetrical disorders.

关键词： Amniotic Fluid Biomarker Interleukin-6 Squamous Cell Carcinoma Antigen

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