The effect of IL-8 secreted by tumor-associated macrophages on colorectal cancer metastasis
10.19405/j.cnki.issn1000–1492.2026.06.002
- VernacularTitle:肿瘤相关巨噬细胞分泌的IL-8对结直肠癌转移的影响
- Author:
Ya SU
1
;
Luyun YUAN
2
;
Qiang ZHANG
1
;
Haijing WANG
3
Author Information
1. Department of Radiotherapy，
2. Department of Traditional Chinese Medicine Oncology，
3. Department of Pharmacy， Putuo District Central Hospital， Shanghai 200062
- Publication Type:Journal Article
- Keywords:
colorectal cancer;
IL-8;
tumor microenvironment;
tumor-associated macrophages;
metastasis;
EMT
- From:
Acta Universitatis Medicinalis Anhui
2026;61(6):978-985
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the role of interleukin （IL）-8 secreted by tumor-associated macrophages （TAMs） in colorectal cancer （CRC） metastasis and its potential therapeutic value. MethodsThe TAMs model was constructed by phorbol ester （PMA） combined with IL-4/IL-13， and the model phenotype was verified by flow cytometry， RT-qPCR and ELISA. Human CRC HCT116 cells were treated with conditioned medium （CM） from M0 macrophages and TAMs， and the metastatic capacity of HCT116 cells was evaluated by wound-healing assay and Transwell assay. The expression levels of IL-8 in M0 macrophages and TAMs were detected by Western blot， RT-qPCR and ELISA. The expression level of epithelial-mesenchymal transition （EMT） markers （E-cadherin， N-cadherin） in HCT116 cells treated with CM-M0 and CM-TAMs were detected by Western blot and RT-qPCR. HCT116 cells were stimulated with CM-TAMs supplemented with IL-8 receptor inhibitor Reparixin. The HCT116 cells metastasis ability was evaluated by wound-healing assay and Transwell assay， and the expression levels of E-cadherin and N-cadherin were detected by Western blot and RT-qPCR. Finally， a splenic injection liver metastasis model was established using murine CRC cells CT26-LUC， and the effect of Reparixin on this animal model was observed by in vivo imaging. ResultsFlow cytometry showed that the proportion of M2 macrophages （CD11b+CD206+ cells） was elevated in the TAMs model. RT-qPCR and ELISA assays revealed that the levels of M2 macrophage markers IL-10 and TGF-βsignificantly increased. Wound-healing assay and Transwell assay demonstrated that CM-TAMs significantly enhanced the migration and invasion ability of HCT116 cells. Western blot， RT-qPCR and ELISA assays showed that TAMs highly expressed IL-8 and simultaneously induced downregulation of E-cadherin and upregulation of N-cadherin in HCT116 cells. Reparixin not only reversed the pro-metastatic effects of CM-TAMs， but also upregulated the expression level of E-cadherin and downregulated that of N-cadherin in HCT116 cells. Furthermore， it reduced the bioluminescence signal intensity of liver metastatic lesions in the splenic injection liver metastasis model. ConclusionThe TAMs promote CRC metastasis by secreting IL-8 to induce EMT. Inhibiting IL-8 secretion in TAMs or blocking the binding of IL-8 to its receptor may provide a new strategy for CRC treatment.
