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01.12.2014 | Research | Ausgabe 1/2014 Open Access

Journal of Experimental & Clinical Cancer Research 1/2014

In silico and Ex vivo approaches identify a role for toll-like receptor 4 in colorectal cancer

Zeitschrift:
Journal of Experimental & Clinical Cancer Research > Ausgabe 1/2014
Autoren:
Daniel A Sussman, Rebeca Santaolalla, Pablo A Bejarano, Monica T Garcia-Buitrago, Maria T Perez, Maria T Abreu, Jennifer Clarke
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1756-9966-33-45) contains supplementary material, which is available to authorized users.

Competing interests

The authors do not have any relevant financial interests related to the work described in this manuscript.

Authors’ contributions

DAS participated in the design of the study, acquired the data, interpreted the data, and drafted the manuscript. RS performed the immunofluorescent and immunohistochemical staining. PAB participated in the interpretation and scoring of immunofluorescence. MTG participated in the interpretation and scoring of immunofluorescence. MTP participated in the interpretation and scoring of immunohistochemical stains. MTA participated in the design of the study and interpretation of results. JC participated in the design of the study, performed the statistical analysis, and interpreted results. All authors participated in the preparation of the manuscript as well as reviewed and approved the final manuscript.

Abstract

Background

Inflammation increases the risk of colorectal cancer (CRC). We and others have described a role for TLR4, the receptor for LPS, in colon cancer. To explore the relationships between TLR4 expression and CRC, we combined the strength of transcriptome array data and immunohistochemical (IHC) staining.

Methods

TLR4 signal intensity was scored in the stromal and epithelial compartments. Detection of differential expression between conditions of interest was performed using linear models, Cox proportional hazards models, and empirical Bayes methods.

Results

A strong association between TLR4 expression and survival was noted, though a dichotomous relationship between survival and specific TLR4 transcripts was observed. Increasing TLR4 expression was seen with advancing tumor stage and was also over-expressed in some adenomas. IHC staining confirmed the positive relationship between TLR4 staining score in the CRC tumor stroma and epithelium with tumor stage, with up to 47% of colon cancer stroma positive for TLR4 staining. Increased TLR4 expression by IHC was also marginally associated with decreased survival. We now also describe that pericryptal myofibroblasts are responsible for a portion of the TLR4 stromal staining.

Conclusions

Increased TLR4 expression occurs early in colonic neoplasia. TLR4 is associated with the important cancer-related outcomes of survival and stage.
Zusatzmaterial
Authors’ original file for figure 1
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Authors’ original file for figure 2
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Authors’ original file for figure 3
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Authors’ original file for figure 4
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Authors’ original file for figure 5
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Authors’ original file for figure 6
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Literatur
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