Cell子刊:细菌易位促进大肠癌肝转移
创作:szx 审核:szx 05月01日
  • CRC患者CD31+内皮细胞中的PV-1+细胞比例高于健康人,且癌组织与癌旁组织的PV-1+细胞比例相似;
  • PV-1高表达与远端转移及更短的无进展生存期相关;
  • 原发肿瘤中可检测到PV-1+细胞的患者的肝转移灶中有更多细菌,定殖于SOX9+高增殖癌细胞附近;
  • CRC小鼠中,肝脏菌群与结肠菌群的相似度高于健康小鼠,且大肠杆菌富集;
  • 大肠杆菌C17通过毒力调节因子VirF驱动小鼠GVB损伤,到达肝脏以促进PMN形成,而抗生素可抑制GVB损伤,以减少CRC的肝转移。
主编推荐语
szx
原发肿瘤产生的因子促进“转移前生态位”(premetastatic niche,PMN)的形成,后者可促进肿瘤的转移。Cancer Cell上发表的一项最新研究发现,结直肠癌(CRC)原发灶中的特定细菌(如大肠杆菌)可破坏肠道血管屏障(GVB),并散播至肝脏促进PMN的形成,以增强对转移癌细胞的招募。在结直肠癌患者中,癌组织与癌旁组织的PV-1(GVB损伤标志物)表达水平均显著升高,并与细菌的肝脏易位、结直肠癌的远端转移及更短的无进展生存期相关。该研究揭示了肠道屏障受损及肠道细菌易位在结直肠癌转移中发挥的重要作用。
关键字
延伸阅读本研究的原文信息和链接出处,以及相关解读和评论文章。欢迎读者朋友们推荐!
图片
Cancer Cell [IF:26.602]

Gut vascular barrier impairment leads to intestinal bacteria dissemination and colorectal cancer metastasis to liver

肠道血管屏障损伤导致肠道细菌散播及结直肠癌肝转移

10.1016/j.ccell.2021.03.004

04-01, Article

Abstract & Authors:展开

Abstract:收起
Metastasis is facilitated by the formation of a “premetastatic niche,” which is fostered by primary tumor-derived factors. Colorectal cancer (CRC) metastasizes mainly to the liver. We show that the premetastatic niche in the liver is induced by bacteria dissemination from primary CRC. We report that tumor-resident bacteria Escherichia coli disrupt the gut vascular barrier (GVB), an anatomical structure controlling bacterial dissemination along the gut-liver axis, depending on the virulence regulator VirF. Upon GVB impairment, bacteria disseminate to the liver, boost the formation of a premetastatic niche, and favor the recruitment of metastatic cells. In training and validation cohorts of CRC patients, we find that the increased levels of PV-1, a marker of impaired GVB, is associated with liver bacteria dissemination and metachronous distant metastases. Thus, PV-1 is a prognostic marker for CRC distant recurrence and vascular impairment, leading to liver metastases.

First Authors:
Alice Bertocchi

Correspondence Authors:
Maria Rescigno

All Authors:
Alice Bertocchi,Sara Carloni,Paola Simona Ravenda,Giovanni Bertalot,Ilaria Spadoni,Antonino Lo Cascio,Sara Gandini,Michela Lizier,Daniele Braga,Francesco Asnicar,Nicola Segata,Chris Klaver,Paola Brescia,Elio Rossi,Achille Anselmo,Silvia Guglietta,Annalisa Maroli,Paola Spaggiari,Noelia Tarazona,Andres Cervantes,Silvia Marsoni,Luca Lazzari,Maria Giovanna Jodice,Chiara Luise,Marco Erreni,Salvatore Pece,Pier Paolo Di Fiore,Giuseppe Viale,Antonino Spinelli,Chiara Pozzi,Giuseppe Penna,Maria Rescigno

评论