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

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

  • Discov Oncol. 2025 Apr 29;16(1):637. doi: 10.1007/s12672-025-02452-z.
Akhmed Aslam # 1,  Bassem Refaat # 2,  Riyad A Almaimani 3,  Ahmad A Obaid 4,  Abdulrahman Mujalli 1,  Wesam F Farrash 1,  Mohamed E Elzubier 3,  Shakir Idris 1,  Afnan Salaka 1,  Ahmed H Almalki 5,  Mofareh Y Alkhaldi 5,  Hassan A Asiri 6,  Mohammad A Baqassi 7,  Ali M Alhanash 8,  Othman M Hakmi 9,  Faisal Minshawi # 10
Affiliations

Affiliations

  • 1 Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Umm Al-Qura University, Prince Sultan Road, Al Abdeyah, PO Box 7607, Makkah, 21955, Kingdom of Saudi Arabia.
  • 2 Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Umm Al-Qura University, Prince Sultan Road, Al Abdeyah, PO Box 7607, Makkah, 21955, Kingdom of Saudi Arabia. barefaat@uqu.edu.sa.
  • 3 Biochemistry Department, Faculty of Medicine, Umm Al-Qura University, Prince Sultan Road, Al Abdeyah, Makkah, 21955, Saudi Arabia.
  • 4 Physiology Department, Faculty of Medicine, Umm Al-Qura University, Prince Sultan Road, Al Abdeyah, Makkah, 21955, Saudi Arabia.
  • 5 Laboratory And Blood Bank Department, Asir Central Hospital, Prince Sultan bin Abdulaziz Road, Al-Rabwah District, Abha, 62523, Saudi Arabia.
  • 6 Forensic Medicine Department, Health Affairs General Directorate in Assir, 7241 Emirate Road, Al Shifa, Abha, 62521, Saudi Arabia.
  • 7 Histopathology Department, King Abdullah Medical City, Muzdalifah Road, Al Mashair, Makkah, 24246, Saudi Arabia.
  • 8 Oncology Department, Asir Central Hospital, Prince Sultan bin Abdulaziz Road, Al-Rabwah District, Abha, 62523, Saudi Arabia.
  • 9 Clinical Laboratory Department, ⁠Security Force Hospital, Al-Baidaa Road, King Fahd Suburb, Dammam, 32314, Saudi Arabia.
  • 10 Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Umm Al-Qura University, Prince Sultan Road, Al Abdeyah, PO Box 7607, Makkah, 21955, Kingdom of Saudi Arabia. fominshawi@uqu.edu.sa.
  • # Contributed equally.
PMID: 40299210 DOI: 10.1007/s12672-025-02452-z
Abstract

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.

Keywords

Apoptosis; Biological therapy; Cell cycle; Colorectal cancer; Interleukin-10 receptor α; Left-right dichotomy; Oncogenesis; STAT3.

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