6533b86dfe1ef96bd12c9728

RESEARCH PRODUCT

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

Ilaria SpadoniAnnalisa MaroliSalvatore PeceSalvatore PeceLuca LazzariMarco ErreniAntonino SpinelliGiovanni BertalotGiuseppe PennaSara CarloniMaria RescignoGiuseppe VialeGiuseppe VialeNoelia TarazonaChris KlaverAntonino Lo CascioElio RossiPaola BresciaAchille AnselmoAndrés CervantesAlice BertocchiPier Paolo Di FiorePier Paolo Di FioreSilvia GugliettaMaria Giovanna JodiceDaniele BragaChiara PozziChiara LuiseSara GandiniPaola Simona RavendaMichela LizierPaola SpaggiariSilvia MarsoniNicola SegataFrancesco Asnicar

subject

0301 basic medicineCancer ResearchColorectal cancerRegulatorVirulencemedicine.disease_causeMetastasis03 medical and health sciences0302 clinical medicinemedicineHumansNeoplasm MetastasisEscherichia coliBacteriabiologybusiness.industryLiver NeoplasmsDistant recurrencebiology.organism_classificationmedicine.disease030104 developmental biologyLiverOncology030220 oncology & carcinogenesisColonic NeoplasmsCancer researchIntestinal bacteriaNeoplasm Recurrence LocalColorectal NeoplasmsbusinessBacteria

description

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. Copyright © 2021 Elsevier Inc. All rights reserved.

yearjournalcountryeditionlanguage
2021-05-01Cancer Cell
https://doi.org/10.1016/j.ccell.2021.03.004