研究人员发现，部分肠菌类细菌能引发结肠癌，这一揭示出这种疾病的一种分子机理的新成果发表在8月在线出版的《自然—医学》期刊上。
Cynthia Sears和同事研究了这样的问题：由产肠毒素脆弱类杆菌（ETBF）导致的肠道定殖如何引发了结肠癌。他们发现，产肠毒素脆弱类杆菌和无毒素脆弱类杆菌都会在小鼠肠道内定殖，但只有产肠毒素脆弱类杆菌会诱发结肠炎症和肿瘤。这些症状与白细胞介素17（IL—17）发出的细胞信号的增加有关。关键是，阻断IL—17或IL—23调节的信号，可抑制产肠毒素脆弱类杆菌诱导的炎症和肿瘤形成。
新发现显示，一种依赖于IL—17的通道与炎症引发型癌症有关，而这种癌症则是由一种普通的肠菌类所致。这一新发现揭示出人类结肠类癌症的一种分子机制，从而打开了一扇治疗这种疾病的大门。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature Medicine 15, 1016 - 1022 (2009) 23 August 2009 | doi:10.1038/nm.2015
A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses
Shaoguang Wu1,8, Ki-Jong Rhee1,7,8, Emilia Albesiano2, Shervin Rabizadeh3,8, Xinqun Wu1,2, Hung-Rong Yen2,4, David L Huso5, Frederick L Brancati1, Elizabeth Wick6, Florencia McAllister1,2, Franck Housseau2, Drew M Pardoll1,2 & Cynthia L Sears1,2
Abstract
The intestinal flora may promote colon tumor formation. Here we explore immunologic mechanisms of colonic carcinogenesis by a human colonic bacterium, enterotoxigenic Bacteroides fragilis (ETBF). ETBF that secretes B. fragilis toxin (BFT) causes human inflammatory diarrhea but also asymptomatically colonizes a proportion of the human population. Our results indicate that whereas both ETBF and nontoxigenic B. fragilis (NTBF) chronically colonize mice, only ETBF triggers colitis and strongly induces colonic tumors in multiple intestinal neoplasia (Min) mice. ETBF induces robust, selective colonic signal transducer and activator of transcription-3 (Stat3) activation with colitis characterized by a selective T helper type 17 (TH17) response distributed between CD4+ T cell receptor- (TCR)+ and CD4–8–TCR+ T cells. Antibody-mediated blockade of interleukin-17 (IL-17) as well as the receptor for IL-23, a key cytokine amplifying TH17 responses, inhibits ETBF-induced colitis, colonic hyperplasia and tumor formation. These results show a Stat3- and TH17-dependent pathway for inflammation-induced cancer by a common human commensal bacterium, providing new mechanistic insight into human colon carcinogenesis.
1 Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
2 Department of Oncology and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
3 Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
4 Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University and Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
5 Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
6 Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
7 Present addresses: Department of Medicine, University of Illinois, Chicago, Illinois, USA (K.-J.R.) and Cedars Sinai Medical Center, Los Angeles, California, USA (S.R.).
8 These authors contributed equally to this work.
