Carcinogenesis Advance Access originally published online on July 14, 2008
Carcinogenesis 2008 29(8):1572-1580; doi:10.1093/carcin/bgn164
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Influence of interleukin-8 and interleukin-10 on sporadic colon cancer development and progression
a
ev*
evi
1
imun Kri
anac2
Division of Molecular Medicine, Ru
er Bokovi Institute, Bijenika cesta 54, 10000 Zagreb, Croatia
1 PLIVA d.d. Research and Development, Ulica grada Vukovara 49, 10000 Zagreb, Croatia
2 Clinical Hospital Dubrava, Avenija Gojka uka 6, 10000 Zagreb, Croatia
* To whom correspondence should be addressed. Tel: +385 1 4561 108; Fax: +385 1 4561 010; Email: tcacev{at}irb.hr
Cytokines produced in the tumour microenvironment have an important role in cancer pathogenesis. Altered cytokine expression may result in increased susceptibility to and/or poor prognosis in certain cancers. Therefore, the aim of this study was to investigate the influence of interleukin (IL)-8 and IL-10 on sporadic colon cancer development and progression. In our study, a statistically significant increase in IL-8 messenger RNA (mRNA) expression and decrease in IL-10 mRNA expression in tumour tissue compared with normal mucous tissue was observed (P = 0.003; P = 1.3 x 10–9). No association was found between IL-8 –251 A/T genotypes and IL-8 mRNA expression in tumour and corresponding normal mucous tissue, as well as susceptibility to sporadic colon cancer. Positive immunohistochemical IL-8 staining was more frequent in moderately and poorly differentiated tumours compared with well-differentiated tumours (P = 0.024). Finally, IL-8 significantly stimulated invasion of HT-29 cells in vitro (P = 0.000172). Significant association of IL-10 –1082 A/G, –819 T/C and –592 A/C genotypes and IL-10 mRNA expression in tumour tissue was observed (P = 0.022; P = 0.013; P = 0.02). Significant association of –819 T/C and –592 A/C genotypes and IL-10 mRNA expression in corresponding normal mucous tissue was observed (P = 0.01; P = 0.04) as well. IL-10 single-nucleotide polymorphism (SNP) promoter genotypes associated with low IL-10 mRNA expression (–819 TT; –592 AA) were also associated with increased risk of sporadic colon cancer compared with high-expression genotypes [odds ratio, 5.53; 95% confidence interval (CI), 1.53–20.1; odds ratio, 4.07; 95% CI, 1.28–12.96]. Positive IL-10 immunohistochemical reaction was more frequent in well-differentiated and moderately differentiated tumours compared with poorly differentiated tumours (P = 0.036). In Dukes’ C tumours, positive IL-10 immunohistochemical reaction was less frequent compared with Dukes’ A and B tumours (P = 0.023). Taken together, our results point to possible tumour promoting role of IL-8 and potential protective role of IL-10 in sporadic colon cancer.
Abbreviations: CI, confidence interval; IL, interleukin; mRNA, messenger RNA; PCR, polymerase chain reaction; RT, reverse transcription; SNP, single-nucleotide polymorphism
Received May 20, 2008; revised July 1, 2008; accepted July 7, 2008.
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