IRCCS Humanitas Research Hospital, via Manzoni 56, Rozzano, Milan 20089, Italy.
IRCCS Humanitas Research Hospital, via Manzoni 56, Rozzano, Milan 20089, Italy; Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini, Pieve Emanuele, MI 20072, Italy.
Cancer Cell. 2021 May 10;39(5):708-724.e11. doi: 10.1016/j.ccell.2021.03.004. Epub 2021 Apr 1.
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.
转移是通过形成“转移前生态位”来促进的，而这个生态位是由原发性肿瘤衍生的因素所培育的。结直肠癌（CRC）主要转移到肝脏。我们表明，肝脏中的转移前生态位是由原发性 CRC 细菌传播诱导的。我们报告称，肿瘤驻留细菌大肠杆菌破坏肠道血管屏障（GVB），GVB 是一种控制细菌沿肠道-肝脏轴传播的解剖结构，这取决于毒力调节因子 VirF。在 GVB 受损后，细菌传播到肝脏，促进转移前生态位的形成，并有利于转移细胞的募集。在 CRC 患者的训练和验证队列中，我们发现，受损 GVB 的标志物 PV-1 水平升高与肝脏细菌传播和同时发生的远处转移有关。因此，PV-1 是 CRC 远处复发和血管损伤的预后标志物，导致肝脏转移。
