Increased protein expression of interleukin-10 and its signalling molecules in colon cancer progression: potential prognostic and therapeutic targets.

BACKGROUND

Interleukin-10 (IL-10) regulates immune responses in solid tumours, but its role in colorectal cancer (CRC) is unclear due to inconsistent findings. Tumour location is a critical prognostic factor, with proximal tumours often linked to worse outcomes. However, the relationship between IL-10 expression and tumour site is poorly understood.

METHODS

Protein expression of IL-10, its α-receptor (IL10Rα), and intracellular signal transducer (STAT3) was measured by immunohistochemistry in archived paired non-cancerous and cancerous colonic specimens collected from the same patients (n = 120). The data were then stratified according to clinical stages (early-stage I/II vs. late-stage III/IV) and tumour sites (right-sided cancers; RSCs vs. left-sided cancers; LSCs). Functional effects of biologically active IL-10 protein (0.1, 1, and 40 ng/ml), anti-IL10Rα monoclonal antibody (0.1, 1, and 40 ng/ml), and a single concentration of a specific STAT3 inhibitor (2 µM) on cell cycle and apoptosis were assessed in HT29 and SW620 CRC cell lines, along with the expression of key regulatory molecules.

RESULTS

Overall, protein expression of IL-10, IL10Rα, and STAT3 was significantly higher in malignant tissues compared to non-malignant tissues. Early and late-stage RSCs exhibited markedly increased expression of these proteins relative to LSCs, with the highest levels observed in late-stage RSCs. Elevated protein levels of all molecules correlated with high-grade tumours, mucinous histology, lymph node metastasis, and advanced cancer stage. While IL-10 treatment showed minimal effects, IL-10Rα blockade or STAT3 inhibition led to cell cycle arrest and apoptosis in HT29 and SW620 cells, associated with increased p21, p27, and Caspase-3, and decreased CCND1, CCND3, PCNA, and survivin gene and protein expression.

CONCLUSIONS

IL-10 and its signalling molecules increased in CRC progression, particularly in RSCs, suggesting their potential oncogenic roles and prognostic significance. Furthermore, targeting IL-10 signalling pathways could offer a promising avenue for CRC treatment. However, further studies are required to explore the IL-10 system in relation to tumour consensus molecular subtypes to better elucidate its biological functions and prognostic values in CRC.