PL3-6 New roles for Interleukin-11 in mucosal immunity and colorectral cancer

Putoczki, Tracy L.; Loving, Andrea; Thiem, Stefan; McKenzie, Brent; Ernst, Matthias

doi:10.1016/j.cyto.2010.07.292

Cited by 1 publication

(2 citation statements)

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“…Our genetic complementation studies highlighted a functional redundancy between the IL‐6 and IL‐11 signalling cascades. Indeed, both cytokines conferred Stat3‐dependent epithelial resistance to DSS‐induced apoptosis and colitis, as well as to CAC‐induced tumourigenesis . Consistent with these observations, IL‐11 administration protects against radiation‐induced mucositis, suggesting that IL‐11 signalling may play an important role in the maintenance of the intestinal epithelium .…”

Section: Promotion Of Gastrointestinal Tumourigenesis By Il‐6 and Il‐11supporting

confidence: 58%

“…Indeed, both cytokines conferred Stat3-dependent epithelial resistance to DSS-induced apoptosis and colitis, as well as to CACinduced tumourigenesis. 40,64 Consistent with these observations, IL-11 administration protects against radiation-induced mucositis, suggesting that IL-11 signalling may play an important role in the maintenance of the intestinal epithelium. 65 Moreover, genetic deficiency for the ligand-binding IL-11Ra subunit completely abrogates gastric tumour formation in compound gp130 Y757F ;il11ra KO mice, and monoallelic il11ra ablation delays the onset and reduces overall gastric tumour burden, which was unaffected when the il6 gene was ablated in these mice.…”

Section: Promotion Of Gastrointestinal Tumourigenesis By Il-6 and Il-11mentioning

confidence: 54%

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Stat3: Linking inflammation to (gastrointestinal) tumourigenesis

Ernst

Putoczki

2012

Clin Exp Pharma Physio

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Tumourigenesis is a multistage process comprising initiation, promotion and progression that is governed by cumulative (epi-)genetic changes. However, tumour initiation, triggered by mutations in proto-oncogenes and/or tumour suppressor genes, is insufficient for the development of cancers. Tumour promotion often depends on the interaction between initiated cells and the microenvironment where an excessive abundance of inflammatory mediators, including those of the interleukin (IL-)6/glycoprotein 130 (gp130) family, promote their expansion. The activity of most soluble mediators ultimately converges on tumour cells through activation of the latent transcription factors nuclear factor (NF)-κB and signal transducer and activator of transcription (Stat) 3 to enhance survival of neoplastic cells. In addition, Stat3 promotes tumour cell proliferation, invasion and induction of an angiogenic switch. Persistent activation of STAT3 is a unifying hallmark of a majority of solid malignancies. However, persistent STAT3 activation usually occurs in the absence of activating mutations in, or amplification of, the STAT3 gene. Instead, it is associated with an oversupply of autocrine and/or paracrine activating cytokines secreted by tumour and stromal cells and comprising (among others) cytokines that use the gp130 receptor. Interleukin-6, IL-11 and other members of the gp130 cytokine family have been identified in preclinical mouse models as promising therapeutic targets for gastrointestinal, hepatic and breast cancers. Thus, pharmacological interference with specific cytokines and tyrosine kinases that trigger Stat3 activation affords opportunities to therapeutically target the non-redundant tumour-promoting signalling function of Stat3.

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Section: Promotion Of Gastrointestinal Tumourigenesis By Il‐6 and Il‐11supporting

confidence: 58%