Abstract & Authors:展开
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.
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