Journal
JOURNAL OF CLINICAL PATHOLOGY
Volume 65, Issue 4, Pages 302-308Publisher
BMJ PUBLISHING GROUP
DOI: 10.1136/jclinpath-2011-200567
Keywords
-
Categories
Funding
- Portuguese Oncology Institute of Porto
Ask authors/readers for more resources
Background Animal data suggest that Toll-like receptors (TLR) may play an important role in colon carcinogenesis. Studies in humans to support that hypothesis are scarce. Aim To evaluate the expression of TLR2, TLR4 and TLR5, and the expression of several other related molecules, in different human colonic lesions. Methods Colon biopsy samples from normal mucosa, normal mucosa adjacent to lesion, adenoma or sporadic carcinoma were obtained from 35 consecutive patients undergoing colonoscopy. Quantification of TLR2, TLR4, TLR5, Toll-interacting protein (TOLLIP), peroxisome proliferator-activated receptor gamma (PPAR-gamma), nuclear factor kappa B, tumour necrosis factor (TNF) alpha, cyclooxygenase (COX) 1 and 2 mRNA was performed by real-time reverse transcription PCR. TLR2, TLR4 and TLR5 protein expression was quantified by immunohistochemistry. Results When compared with normal mucosa (1.0 arbitrary unit (AU)), adjacent normal mucosa presented higher expression of COX-2 (1.86 +/- 0.3 AU, p=0.01) and TNF alpha (1.44 +/- 0.18 AU, p=0.04) and lower TOLLIP expression (0.75 +/- 0.05 AU, p=0.004). Adenomas and carcinomas presented higher expression of COX-2 (1.63 +/- 0.27 and 1.38 +/- 0.14 AU, p=0.03 and p=0.05, respectively) and lower expression of TOLLIP (0.44 +/- 0.04 AU, p<0.001), with diffuse and higher TLR protein expression (p<0.001). Carcinomas also expressed higher TLR2 (2.31 +/- 0.32 AU, p=0.006) and lower PPAR-gamma (0.56 +/- 0.12 AU, p=0.003). There was a trend towards decreased TOLLIP (p<0.001) and PPAR-gamma (p=0.05) from normal mucosa to adenoma/carcinoma. Conclusions Persistently positive TLR expression and lower expression of TLR inhibitors was associated with higher TLR protein levels throughout the spectrum of lesions of colon carcinogenesis. Increasing activation of these receptors by bacteria may play a crucial role in colon carcinogenesis and tumour progression.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available