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

被引：365

作者：

Bertocchi, Alice ^{[1
]}

Carloni, Sara ^{[1
,2
]}

Ravenda, Paola Simona ^{[3
]}

Bertalot, Giovanni ^{[3
]}

Spadoni, Ilaria ^{[1
,2
]}

Lo Cascio, Antonino ^{[1
,2
]}

Gandini, Sara ^{[3
]}

Lizier, Michela ^{[1
]}

Braga, Daniele ^{[1
]}

Asnicar, Francesco ^{[4
]}

Segata, Nicola ^{[4
]}

Klaver, Chris ^{[3
,9
]}

Brescia, Paola ^{[1
]}

Rossi, Elio ^{[5
]}

Anselmo, Achille ^{[1
]}

Guglietta, Silvia ^{[3
,10
,11
]}

Maroli, Annalisa ^{[1
]}

Spaggiari, Paola ^{[1
]}

Tarazona, Noelia ^{[6
]}

Cervantes, Andres ^{[6
]}

Marsoni, Silvia ^{[7
]}

Lazzari, Luca ^{[7
]}

Jodice, Maria Giovanna ^{[3
]}

Luise, Chiara ^{[3
,12
]}

Erreni, Marco ^{[1
]}

Pece, Salvatore ^{[3
,8
]}

Di Fiore, Pier Paolo ^{[3
,8
]}

Viale, Giuseppe ^{[3
,8
]}

Spinelli, Antonino ^{[1
,2
]}

Pozzi, Chiara ^{[1
]}

Penna, Giuseppe ^{[1
]}

Rescigno, Maria ^{[1
,2
]}

机构：

[1] IRCCS Humanitas Res Hosp, Via Manzoni 56, I-20089 Milan, Italy

[2] Humanitas Univ, Dept Biomed Sci, Via Rita Levi Montalcini, I-20072 Pieve Emanuele, MI, Italy

[3] IEO European Inst Oncol IRCCS, I-20141 Milan, Italy

[4] Univ Trento, CIBIO Dept, Trento, Italy

[5] Univ Milan, Dept Biosci, Via Celoria 26, I-20133 Milan, Italy

[6] Univ Valencia, Hosp Clin Univ, Biomed Res Inst INCLIVA, Dept Med Oncol, Valencia, Spain

[7] IFOM, Via Adamello 16, I-20139 Milan, MI, Italy

[8] Univ Milan, Dept Oncol & Hematooncol, I-20142 Milan, Italy

[9] Netherlands Canc Inst, Div Tumor Biol & Immunol, Amsterdam, Netherlands

[10] Med Univ South Carolina, 173 Ashley Ave 29,425, Charleston, SC 29425 USA

[11] Hollings Canc Ctr, Dept Microbiol & Immunol, 173 Ashley Ave 29,425, Charleston, SC 29425 USA

[12] Tethis SPA, Milan, Italy

来源：

CANCER CELL | 2021年 / 39卷 / 05期

基金：

欧洲研究理事会;

关键词：

MICROBIOTA; RECEPTOR; CELLS;

D O I：

10.1016/j.ccell.2021.03.004

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：708 / +

页数：28

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