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

Journal article

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.

Authors: Bertocchi, A; Carloni, S; Ravenda, PS; Bertalot, G; Spadoni, I

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Cell Press
• Journal: Cancer Cell
• Volume: 39
• Issue: 5
• Pages: 708-724
• Place of publication: United States
• Publication date: 2021-04-01
• Acceptance date: 2021-03-08
• DOI: 10.1016/j.ccell.2021.03.004
• EISSN: 1878-3686
• ISSN: 1535-6108
• Pmid: 33798472
• Language: English
• Keywords: neoplasm metastasis; colo-rectal cancer; cancer; digestive diseases; colonic neoplasms; microbiome; bacteria; liver neoplasms; oral and gastrointestinal; women's health; liver disease; neoplasm recurrence; local; liver; colorectal neoplasms