The membrane-bound mucins: From cell signalling to transcriptional regulation and expression in epithelial cancers

Jonckheere, Nicolas; Seuningen, Isabelle Van

doi:10.1016/j.biochi.2009.09.018

Cited by 117 publications

(116 citation statements)

References 134 publications

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“…VSV has never been tested in any immunocompetent model of pancreatic cancer. We have utilized a system that allows the study of oncolytic viruses (VSV or other OVs) in the context of MUC1 overexpression, as seen in approximately 80% of PDA patients, or no expression (49,50). Our data show that VSV can infect and kill all tested mouse PDA cell lines in vitro and cause transient reduction of KCM and KCKO tumors in vivo.…”

Section: Discussionmentioning

confidence: 94%

Oncolytic Vesicular Stomatitis Virus in an Immunocompetent Model of MUC1-Positive or MUC1-Null Pancreatic Ductal Adenocarcinoma

Hastie

Besmer

Shah

et al. 2013

J Virol

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Vesicular stomatitis virus (VSV) is a promising oncolytic agent against various malignancies. Here, for the first time, we tested VSV in vitro and in vivo in a clinically relevant, immunocompetent mouse model of pancreatic ductal adenocarcinoma (PDA). Our system allows the study of virotherapy against PDA in the context of overexpression (80% of PDA patients) or no expression of human mucin 1 (MUC1), a major marker for poor prognosis in patients. In vitro, we tested three VSV recombinants, wildtype VSV, VSV-green fluorescent protein (VSV-GFP), and a safe oncolytic VSV-⌬M51-GFP, against five mouse PDA cell lines that either expressed human MUC1 or were MUC1 null. All viruses demonstrated significant oncolytic abilities independent of MUC1 expression, although VSV-⌬M51-GFP was somewhat less effective in two PDA cell lines. In vivo administration of VSV-⌬M51-GFP resulted in significant reduction of tumor growth for tested mouse PDA xenografts (؉MUC1 or MUC1 null), and antitumor efficacy was further improved when the virus was combined with the chemotherapeutic drug gemcitabine. The antitumor effect was transient in all tested groups. The developed system can be used to study therapies involving various oncolytic viruses and chemotherapeutics, with the goal of inducing tumor-specific immunity while preventing premature virus clearance.

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Section: Discussionmentioning

confidence: 94%

Oncolytic Vesicular Stomatitis Virus in an Immunocompetent Model of MUC1-Positive or MUC1-Null Pancreatic Ductal Adenocarcinoma

Hastie

Besmer

Shah

et al. 2013

J Virol

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“…This gene expression was confirmed by immunohistochemical analysis for muc4, which only showed detectible protein expression in H. felis-infected B6.SPF (data not shown) (Schmitz et al 2009). Muc4 is known to encode a membrane-bound mucin that is overexpressed in many adenocarcinomas (Jonckheere and Van Seuningen 2010;Senapati et al 2008). Muc4 overexpression can increase tumorgenicity of transplanted gastric AGS cells and phosphorylated ErbB2 (Senapati et al 2008).…”

Section: Discussionmentioning

confidence: 99%

Helicobacter felis–Associated Gastric Disease in Microbiota-Restricted Mice

Schmitz

Durham²,

Schoeb³

et al. 2011

J Histochem Cytochem.

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SummaryHuman Helicobacter pylori infection leads to multiple pathological consequences, including gastritis and adenocarcinoma. Although this association has led to the classification of H. pylori as a type 1 carcinogen, it is not clear if additional nonhelicobacter gastric microbiota play a role in these diseases. In this study, we utilized either specific pathogen-free C57BL/6 mice (B6.SPF) or mice colonized with altered Schaedler flora (B6.ASF) to evaluate the role of nonhelicobacter gastric microbiota in disease development after Helicobacter felis infection. Despite similar histological changes, H. felis persisted in B6.ASF stomachs, while H. felis could no longer be detected in the majority of B6.SPF mice. The B6.SPF mice also acquired multiple Lactobacillus spp. in their stomachs after H. felis infection. Our data indicate that potential mechanisms responsible for the ineffective H. felis clearance in the B6.ASF model include the absence of new gastric microbiota to compete for the gastric niche, the lack of expression of new gastric mucins, and a reduced ratio of H. felis-specific IgG2c:IgG1 serum antibodies. These data suggest that although H. felis is sufficient to initiate gastric inflammation and atrophy, bacterial eradication and the systemic immune response to infection are significantly influenced by pre-existing and acquired gastric microbiota. (J Histochem Cytochem 59:826-841, 2011)

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“…In this manner, a chronic inflammatory condition can theoretically turn the effects of transmembrane mucins against the cells they normally protect. Evidence supporting this assertion can be observed in a number of adenocarcinomas, where specific transmembrane mucins are often overexpressed (Jonckheere and Van Seuningen, 2010). The usual protective effects of mucins in epithelial cells with normal physiologic adhesion patterns become reversed in cancers by a perturbed glycosylation signature.…”

Section: Altered Glycosylation Of Epithelial Mucinsmentioning

confidence: 91%