Carcinogenesis Advance Access published online on July 14, 2008
Carcinogenesis, doi:10.1093/carcin/bgn164
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Influence of interleukin-8 and interleukin-10 on sporadic colon cancer development and progression
a
ev1
evi
2
imun Kri
anac31
1 Division of Molecular Medicine, Ru
er Bokovi Institute, Bijenika cesta 54, 10000 Zagreb, Croatia
2 PLIVA d.d. Research and Development, Ulica grada Vukovara 49, 10000 Zagreb, Croatia
3 Clinical Hospital Dubrava, Avenija Gojka uka 6, 10000 Zagreb, Croatia
Address for correspondence: Tamara aev, Ph.D., Division of Molecular Medicine, Ruer Bokovi Institute, Bijenika c. 54, HR-10000 Zagreb, CROATIA. Tel:+385-1-4561-108. Fax:+385-1-4561-010. E-mail: 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-8 and interleukin-10 on sporadic colon cancer development and progression.
In our study, a statistically significant increase in IL-8 mRNA expression and decrease in IL-10 mRNA expression in tumour tissue compared to normal mucous tissue was observed (p=0.003; p = 1.3x10-9). No association was found between IL-8 -251A/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 to well differentiated tumours (p = 0.024). Finally, interleukin-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 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 to high expression genotypes (5.53, 95% CI, 1.53-20.1; 4.07, 95% CI, 1.28-12.96). Positive IL-10 immunohistochemical reaction was more frequent in well- and moderately differentiated tumours compared to poorly differentiated tumours (p = 0.036). In Dukes’ C tumours positive IL-10 immunohistochemical reaction was less frequent compared to Dukes’ A and B tumours (p = 0.023). Taken together our results point to possible tumour promoting role of interleukin-8 and potential protective role of interleukin-10 in sporadic colon cancer.
Key Words: interleukin-8 • interleukin-10 • polymorphism • mRNA expression • immunohistochemistry • colon cancer
Received May 20, 2008; revised July 1, 2008; accepted July 7, 2008.