第三军医大学:高脂饮食竟能抑制大肠癌腹膜转移?
创作:Lexi 审核:Lexi 2020年10月26日
  • 建立模拟腹膜转移的CRC小鼠模型,发现高脂饮食(HFD)可抑制癌细胞向脂肪组织转移,提高小鼠生存率;
  • HFD刺激脂肪组织巨噬细胞(ATMs)向M1样表型活化,并以TLR4依赖的方式增强ATM对癌细胞的吞噬能力;
  • ATMs中TLR4-Cxcl10轴促进癌细胞转移的脂肪中T细胞募集和活化;
  • 消融巨噬细胞、T细胞失活或阻断巨噬细胞TLR4-Cxcl10轴可抑制HFD对癌细胞转移的抑制作用;
  • HFD和常规化疗药物(奥沙利铂或5-氟尿嘧啶)协同提高小鼠生存。
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Lexi
结直肠癌(CRC)的腹膜种植转移(PC)是终末期的恶性肿瘤,且没有有效策略来预防这种情况。来自重庆第三军医大学的缪洪明研究团队在Signal Transduction and Targeted Therapy发表最新研究,发现早期高脂饮食(HFD)的短期治疗可以抑制CRC的腹膜种植,这为CRC患者的临床管理提供新的思路。
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Dietary fats suppress the peritoneal seeding of colorectal cancer cells through the TLR4/Cxcl10 axis in adipose tissue macrophages

膳食脂肪通过脂肪组织巨噬细胞的TLR4/Cxcl10轴抑制结直肠癌细胞在腹膜种植

10.1038/s41392-020-00327-z

2020-10-15, Article

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Peritoneal carcinomatosis (PC) of colorectal cancer (CRC) is a terminal phase of malignancy with no effective strategies for the prevention of this condition. Here we established PC models in mice by intraperitoneal engraftment of CRC cells and revealed an unexpected role for a high-fat diet (HFD) in preventing metastatic seeding in the visceral fat. Mechanistically, the HFD stimulated the activation of adipose tissue macrophages (ATMs) toward an M1-like phenotype and enhanced ATM tumor phagocytosis in a TLR4-dependent manner. Furthermore, the TLR4–Cxcl10 axis in ATMs promoted T cell recruitment, and M1-like macrophages stimulated T cell activation in tumor-seeded fats. The inhibitory effect of the HFD on tumor seeding was abolished with the ablation of macrophages, inactivation of T cells, or blockade of the TLR4–Cxcl10 axis in macrophages. Finally, we showed that a HFD and conventional chemotherapeutic agents (oxaliplatin or 5-fluorouracil) synergistically improved the survival of tumor-seeded mice. Collectively, our findings demonstrate that peritoneal seeding of CRC can be suppressed by short-term treatment with a HFD in the early phase, providing a novel concept for the management of these patients in the clinic.

First Authors:
Wei Xiang,Rongchen Shi

Correspondence Authors:
Hongming Miao

All Authors:
Wei Xiang,Rongchen Shi,Dapeng Zhang,Xia Kang,Lili Zhang,Jing Yuan,Xuan Zhang,Hongming Miao

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