Induction of inflammatory bowel disease accelerates adenoma formation in Min +/− mice

Huang, Emina H.; Park, Juliet C.; Appelman, Henry D.; Weinberg, Alan; Banerjee, Mousumi; Logsdon, Craig D.; Schmidt, Ann Marie

doi:10.1016/j.surg.2005.11.005

Cited by 18 publications

(15 citation statements)

References 22 publications

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“…In this transgenic model, the incidence of chronic inflammatory enterocolitis is as high as 60% in some environments, with an incidence of dysplastic lesions of up to 30% [88]. Furthermore, breeding the MIN+/-mouse with the IL-10 null mouse caused a dramatic increase in both inflammation and colonic polyps, supporting a role for inflammation in neoplasia [89]. The administration of sRAGE was able to ameliorate the inflammation observed in the IL-10 null mouse model [15].…”

Section: Colon Cancermentioning

confidence: 77%

RAGE and RAGE Ligands in Cancer

Logsdon

Fuentes

Huang

et al. 2007

CMM

187

170

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The receptor for advanced glycation end-products (RAGE) is a multifunctional receptor with multiple ligands that is known to play a key role in several diseases, including diabetes, arthritis, and Alzheimer's disease. Recent evidence indicates that this receptor also has an important role in cancer. RAGE ligands, which include the S100/calgranulins and high-mobility group box 1 (HMGB1) ligands, are expressed and secreted by cancer cells and are associated with increased metastasis and poorer outcomes in a wide variety of tumors. These ligands can interact in an autocrine manner to directly activate cancer cells and stimulate proliferation, invasion, chemoresistance, and metastasis. RAGE ligands derived from cancer cells can also influence a variety of important cell types within the tumor microenvironment, including fibroblasts, leukocytes, and vascular cells, leading to increased fibrosis, inflammation, and angiogenesis. Several of the cells in the tumor microenvironment also produce RAGE ligands. Most of the cancer-promoting effects of RAGE ligands are the result of their interaction with RAGE. However, these ligands also often have separate intracellular roles, and some may interact with other extracellular targets, so it is not currently possible to assign all of their effects to RAGE activation. Despite these complications, the bulk of the evidence supports the premise that the ligand-RAGE axis is an important target for therapeutic intervention in cancer.

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Section: Colon Cancermentioning

confidence: 77%

RAGE and RAGE Ligands in Cancer

Logsdon

Fuentes

Huang

et al. 2007

CMM

187

170

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“…A general pro-tumorigenic role for the microbiota was demonstrated in the Apc Min/+ model, as the mice display reduced tumor load in the small and/or large intestine when derived under germ-free (GF) conditions (9,10). Noticeably, inflammation also enhances development of colon cancer in this model, as seen with the use of dextran sulfate sodium (DSS) (11), by specifically deleting the Apc gene in epithelial cells (12), and by genetically introducing defective IL-10 signaling (13–15). Inflammation and colonic polyposis in mice with Apc deficiency and T cell-specific deletion of Il10 , Apc Δ468 ;CD4 Cre Il10 f/f mice, can be attenuated by antibiotic treatment (14), suggesting that microbiota-driven inflammation underlies colitis-associated CRC.…”

Section: Introductionmentioning

confidence: 99%

Locoregional Effects of Microbiota in a Preclinical Model of Colon Carcinogenesis

et al. 2017

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Inflammation and microbiota are critical components of intestinal tumorigenesis. To dissect how the microbiota contributes to tumor distribution, we generated germ-free (GF) ApcMin/+ and ApcMin/+;Il10−/− mice and exposed them to specific-pathogen-free (SPF) or colorectal cancer-associated bacteria. We found colon tumorigenesis significantly correlated with inflammation in SPF housed ApcMin/+;Il10−/−, but not ApcMin/+ mice. In contrast, small intestinal neoplasia development significantly correlated with age in both ApcMin/+;Il10−/− and ApcMin/+ mice. GF ApcMin/+;Il10−/− mice conventionalized by an SPF microbiota had significantly more colon tumors compared to GF mice. Gnotobiotic studies revealed that while Fusobacterium nucleatum clinical isolates with FadA and Fap2 adhesins failed to induce inflammation and tumorigenesis, pks+ Escherichia coli promoted tumorigenesis in the ApcMin/+;Il10−/− model in a colibactin-dependent manner, suggesting colibactin is a driver of carcinogenesis. Our results suggest a distinct etiology of cancers in different locations of the gut, where colon cancer is primarily driven by inflammation and the microbiome, while age is a driving force for small intestine cancer.

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“…The PA system takes part in the inflammatory processes [24] and uPA has been implicated in the early stages of colonic tumour development [25]. In experimental murine models, the induction of an inflammatory bowel disease accelerates adenoma formation [26] whereas a uPA deficiency diminishes their frequency and impairs leukocyte infiltration. [27] The molecular pathways involved in cell survival and proliferation and linking inflammatory cells to altered epithelial cells may be regulated by the tissue context in which tumour cells may or may not progress [28].…”

Section: Discussionmentioning

confidence: 99%

The Plasminogen System in Microdissected Colonic Mucosa Distant from an Isolated Adenoma

Saucy

Bachmann

Peterman³

et al. 2010

Pathol. Oncol. Res.

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In the colon, the urokinase-type plasminogen activator (uPA), its receptor (uPAR), and plasminogen activator inhibitors, PAI-1 and PAI-2, are implicated in the transition from mucosa to adenoma and tumour progression. However, expression in the mucosa adjacent, or distant, to an adenoma has not yet been investigated. Three biopsies from mucosae adjacent (20 cm, ipsilateral) and distant (contralateral) to an isolated tubular adenoma were analysed in 14 patients and 8 controls. Laser microdissection isolated stromal and epithelial crypt components, and quantitative RT-PCR analyses of uPA, uPAR, PAI-1 and PAI-2 mRNA levels were performed. Among controls, no significant differences in the markers were noted. With left colon isolated tubular adenoma, uPA, uPAR, and PAI-2 mRNA levels were significantly increased in the adjacent mucosal stroma compared to epithelial crypt levels (p < 0.05). In right colon adenoma, the mRNA levels of these 3 molecular markers were significantly increased only in the adjacent mucosal stromal samples (p < 0.05). Isolated tubular adenoma in the colon increases significantly the mRNA levels of 3 proteolysis-associated molecular markers in the stromal, but not in the epithelial, components of adjacent mucosa. These results suggest the presence of regional and dynamic interactions in apparently non-involved mucosae.

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Induction of inflammatory bowel disease accelerates adenoma formation in Min +/− mice

Cited by 18 publications

References 22 publications

RAGE and RAGE Ligands in Cancer

RAGE and RAGE Ligands in Cancer

Locoregional Effects of Microbiota in a Preclinical Model of Colon Carcinogenesis

The Plasminogen System in Microdissected Colonic Mucosa Distant from an Isolated Adenoma

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