Fusobacterium nucleatum Potentiates Intestinal Tumorigenesis and Modulates the Tumor-Immune Microenvironment

被引：2082

作者：

Kostic, Aleksandar D. ^{[1
,2
,3
,4
]}

Chun, Eunyoung ^{[5
,6
]}

Robertson, Lauren ^{[5
,6
]}

Glickman, Jonathan N. ^{[1
,2
,7
]}

Gallini, Carey Ann ^{[5
,6
]}

Michaud, Monia ^{[5
,6
]}

Clancy, Thomas E. ^{[1
,2
,3
,8
]}

Chung, Daniel C. ^{[1
,2
,9
]}

Lochhead, Paul ^{[10
]}

Hold, Georgina L. ^{[10
]}

El-Omar, Emad M. ^{[10
]}

Brenner, Dean ^{[11
]}

Fuchs, Charles S. ^{[1
,2
,3
,5
,6
]}

Meyerson, Matthew ^{[1
,2
,3
,4
]}

Garrett, Wendy S. ^{[1
,2
,3
,4
,5
,6
]}

机构：

[1] Harvard Univ, Sch Med, Dept Med, Dept Pathol, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA

[3] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[4] Broad Inst Harvard & MIT, Canc Program, Cambridge, MA 02142 USA

[5] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA

[6] Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA

[7] Miraca Life Sci Inc, Newton, MA 02464 USA

[8] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA

[9] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA

[10] Univ Aberdeen, Sch Med & Dent, Aberdeen AB25 2ZD, Scotland

[11] Univ Michigan, Med Ctr, Canc & Geriatr Ctr, Ann Arbor, MI 48109 USA

来源：

CELL HOST & MICROBE | 2013年 / 14卷 / 02期

关键词：

REGULATORY T-CELLS; NF-KAPPA-B; COLORECTAL-CANCER; MICROBIAL PRODUCTS; BET DEFICIENCY; INFLAMMATION; ACTIVATION; BACTERIA; INNATE;

D O I：

10.1016/j.chom.2013.07.007

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Increasing evidence links the gut microbiota with colorectal cancer. Metagenomic analyses indicate that symbiotic Fusobacterium spp. are associated with human colorectal carcinoma, but whether this is an indirect or causal link remains unclear. We find that Fusobacterium spp. are enriched in human colonic adenomas relative to surrounding tissues and in stool samples from colorectal adenoma and carcinoma patients compared to healthy subjects. Additionally, in the Apc(Min/+) mouse model of intestinal tumorigenesis, Fusobacterium nucleatum increases tumor multiplicity and selectively recruits tumor-infiltrating myeloid cells, which can promote tumor progression. Tumors from Apc(Min/+) mice exposed to F. nucleatum exhibit a proinflammatory expression signature that is shared with human fusobacteria-positive colorectal carcinomas. However, unlike other bacteria linked to colorectal carcinoma, F. nucleatum does not exacerbate colitis, enteritis, or inflammation-associated intestinal carcinogenesis. Collectively, these data suggest that, through recruitment of tumor-infiltrating immune cells, fusobacteria generate a proinflammatory microenvironment that is conducive for colorectal neoplasia progression.

引用

页码：207 / 215

页数：9

共 40 条

[1] Intestinal Inflammation Targets Cancer-Inducing Activity of the Microbiota [J].