意大利IRCCS人文研究医院Maria Rescigno研究团队取得最新进展。他们发现肠血管屏障障碍导致肠道细菌扩散和结直肠癌（CRC）转移到肝脏。相关论文发表在2021年4月1日出版的《癌细胞》杂志上。

他们显示肝脏中的转移前微环境是由细菌从主要CRC传播所诱导。他们报告肿瘤驻留细菌大肠埃希氏菌破坏肠道血管屏障（GVB），解剖结构控制沿肠道-肝轴的细菌传播，具体取决于毒力调节剂VirF。在GVB受损时，细菌会扩散到肝脏，促进转移前微环境的形成，并有利于转移细胞的募集。

在CRC患者的训练和验证队列中，他们发现PV-1（GVB受损的标志物）水平的升高与肝细菌的传播和远距离转移有关。因此，PV-1是CRC远距离转移复发和血管受损，并导致肝转移的预后标志物。

研究人员表示，“转移前微环境”的形成促进了转移，这是由原发性肿瘤来源的因子促进的。CRC主要转移到肝脏。

附：英文原文

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

Author: 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

Issue&Volume: 2021-04-01

Abstract: Metastasis is facilitated by the formation of a “premetastatic niche,” which is fosteredby primary tumor-derived factors. Colorectal cancer (CRC) metastasizes mainly to theliver. We show that the premetastatic niche in the liver is induced by bacteria disseminationfrom primary CRC. We report that tumor-resident bacteria Escherichia coli disrupt the gut vascular barrier (GVB), an anatomical structure controlling bacterialdissemination along the gut-liver axis, depending on the virulence regulator VirF.Upon GVB impairment, bacteria disseminate to the liver, boost the formation of a premetastaticniche, and favor the recruitment of metastatic cells. In training and validation cohortsof 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.

DOI: 10.1016/j.ccell.2021.03.004

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(21)00162-8