Promotion of Hepatocellular Carcinoma by the Intestinal Microbiota and TLR4

Dapito, Dianne H.; Mencin, Ali; Gwak, Geum‐Youn; Pradère, Jean‐Philippe; Jang, Myoung-Kuk; Mederacke, Ingmar; Caviglia, Jorge Matías; Khiabanian, Hossein; Adeyemi, Adebowale; Bataller, Ramón; Lefkowitch, Jay H.; Bower, Maureen A.; Friedman, Richard A.; Sartor, R. Balfour; Rabadán, Raúl; Schwabe, Robert F.

doi:10.1016/j.ccr.2012.02.007

Cited by 1,115 publications

(1,137 citation statements)

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“…The laboratory mouse has been instrumental for establishing roles for the gut microbiota in many aspects of mammalian physiology: angiogenesis (Stappenbeck et al 2002;Reinhardt et al 2012), bone mineral density (Cho et al 2012;Sjö gren et al 2012), brain development and behavior (Sudo et al 2004;Bravo et al 2011;Diaz Heijtz et al 2011;Ezenwa et al 2012), obesity and malnutrition Smith et al 2013), hepatic function (Dapito et al 2012;Henao-Mejia et al 2012), intestinal response to injury and repair (Rakoff-Nahoum et al 2004; Swanson et al 2011), and innate and adaptive immune function (for reviews, see Garrett et al 2010b;Littman and Pamer 2011;Hooper et al 2012). Ninety-nine percent of mouse genes are shared with humans at the host genetic level, and they share key similarities with the human gut microbiome at the phylum through family levels ( Fig.…”

Section: Micementioning

confidence: 99%

Exploring host–microbiota interactions in animal models and humans

2013

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The animal and bacterial kingdoms have coevolved and coadapted in response to environmental selective pressures over hundreds of millions of years. The meta'omics revolution in both sequencing and its analytic pipelines is fostering an explosion of interest in how the gut microbiome impacts physiology and propensity to disease. Gut microbiome studies are inherently interdisciplinary, drawing on approaches and technical skill sets from the biomedical sciences, ecology, and computational biology. Central to unraveling the complex biology of environment, genetics, and microbiome interaction in human health and disease is a deeper understanding of the symbiosis between animals and bacteria. Experimental model systems, including mice, fish, insects, and the Hawaiian bobtail squid, continue to provide critical insight into how host-microbiota homeostasis is constructed and maintained. Here we consider how model systems are influencing current understanding of host-microbiota interactions and explore recent human microbiome studies.The distinctive body plans of animals offer many niches for members of the archaeal and bacterial kingdoms. While the lumen of the human distal gut is one of the most densely populated ecosystems on our planet, humans and other animals harbor several microbiomes on and within their body surfaces such as the respiratory and urogenital tracts and the skin. As the gut has evolved from the relatively simple tube of the ancient cyclostomatida to the more highly compartmentalized gastrointestinal tracts of mammalian species, the diversity and complexity of the microbial inhabitants of those spaces has increased as well (Fig.

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Section: Micementioning

confidence: 99%

Exploring host–microbiota interactions in animal models and humans

2013

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“…Previous studies have reported pro-tumorigenic effects for different TLRs, such as TLR2 14–18 , TLR4 19–23 , TLR5 24 , TLR7 10,11,25 and TLR9 26–30 . In prostate and breast cancer, the stimulation of TLR9 induced an over-expression of matrix metalloproteinase 13 as well as an increase of cell invasion 31,32 .…”

Section: Discussionmentioning

confidence: 99%

Toll like receptor 7 expressed by malignant cells promotes tumor progression and metastasis through the recruitment of myeloid derived suppressor cells

et al. 2018

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In non-small cell lung carcinoma (NSCLC), stimulation of toll-like receptor 7 (TLR7), a receptor for single stranded RNA, is linked to tumor progression and resistance to anticancer chemotherapy. However, the mechanism of this effect has been elusive. Here, using a murine model of lung adenocarcinoma, we demonstrate a key role for TLR7 expressed by malignant (rather than by stromal and immune) cells, in the recruitment of myeloid derived suppressor cells (MDSCs), induced after TLR7 stimulation, resulting in accelerated tumor growth and metastasis. In adenocarcinoma patients, high TLR7 expression on malignant cells was associated with poor clinical outcome, as well as with a gene expression signature linked to aggressiveness and metastastic dissemination with high abundance of mRNA encoding intercellular adhesion molecule 1 (ICAM-1), cytokeratins 7 and 19 (KRT-7 and 19), syndecan 4 (SDC4), and p53. In addition, lung tumors expressing high levels of TLR7 have a phenotype of epithelial mesenchymal transition with high expression of vimentin and low abundance of E-cadherin. These data reveal a crucial role for cancer cell-intrinsic TLR7 expression in lung adenocarcinoma progression.

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“…La translocation de bactéries intestinales est une caractéristique des maladies chroniques hépatiques et contribue à l'inflammation et la fibrose. Le microbiote intestinal et le TLR4, récepteur impliqué dans la reconnaissance des produits bactériens, participent ainsi au développement d'HCC [18]. Un métabolite produit par les bactéries, le propionate, possède en revanche la capacité de réduire la prolifération cellulaire dans le cancer du foie [19].…”

Section: Microbiote Et Immunité Intestinaleunclassified