title: Influence of interleukin-8 and interleukin-10 on sporadic colon cancer development and progression.
abstract: 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.
authors.affiliation: Division of Molecular Medicine, Ruder Bosković Institute, Bijenicka cesta 54, 10000 Zagreb, Croatia. tcacev@irb.hr
authors.forename: Tamara
authors.initials: T
authors.lastname: Cacev
authors.forename: Senka
authors.initials: S
authors.lastname: Radosević
authors.forename: Simun
authors.initials: S
authors.lastname: Krizanac
authors.forename: Sanja
authors.initials: S
authors.lastname: Kapitanović
mesh_terms: D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D016209:Interleukin-8 / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016209:Interleukin-8; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016753:Interleukin-10