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

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.

Keywords: Escherichia coli; bacteria; colorectal cancer; gut vascular barrier; inflammatory monocytes; macrophages; metastases; neutrophils; premetastatic niche; vasculature.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacteria / isolation & purification
  • Colonic Neoplasms / blood supply
  • Colonic Neoplasms / pathology
  • Colorectal Neoplasms / blood supply*
  • Colorectal Neoplasms / pathology*
  • Humans
  • Liver / pathology
  • Liver Neoplasms / pathology*
  • Liver Neoplasms / secondary
  • Neoplasm Metastasis / pathology*
  • Neoplasm Recurrence, Local / pathology*