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Oct4 Induces IL-17A: M2 Polarization in Cervical Cancer

March, 03, 2024 | Cervical Cancer, Gynecologic Cancer

KEY TAKEAWAYS

  • The study aimed to explore how IL-17A influences M2 macrophage polarization and its mechanism in cervical cancer progression.
  • The results demonstrated that Oct4 initiates IL-17A production, fostering M2 macrophage polarization and thereby enhancing cervical cancer cell metastasis.

Cervical cancer, a prevalent malignancy in females, involves interleukin (IL)-17A, known for its pro-inflammatory role in diseases including cancer. While M2 macrophages promote tumor growth, it remains unclear if IL-17A induces their polarization in cervical cancer.

Zhuoqiong Bian and the team spearheaded the study that aimed to explore how IL-17A influences M2 macrophage polarization and the underlying mechanisms in cervical cancer progression.

The study utilized RT-qPCR to examine IL-17A expression in cancer tissues and cells. Flow cytometry assessed M1/M2 macrophage polarization. Colony formation and transwell assays gauged cell proliferative, migratory, and invasive abilities. ChIP and luciferase reporter assays investigated the IL-17A and octamer-binding transcription factor 4 (OCT4) interaction.

The results demonstrated that IL-17A expression and concentration were elevated in metastatic cervical cancer tissues and cells. Additionally, IL-17A was found to promote M2 macrophage polarization in cervical cancer. Moreover, IL-17A facilitated the promotion of cervical cancer cell proliferation, migration, and invasion by macrophages. Mechanistic assays revealed that Oct4 binds to and transcriptionally activates IL-17A in cervical cancer cells.

Furthermore, Oct4 promoted the malignant phenotype of cervical cancer cells and M2 macrophage polarization by activating the p38 pathway, which upregulated IL-17A. Additionally, in vivo experiments confirmed that Oct4 knockdown reduced tumor growth and metastasis. 

The study concluded that Oct4 induces IL-17A, promoting M2 macrophage polarization, thereby facilitating cervical cancer cell metastasis.

This research received support from the National Natural Science Foundation of China and the Natural Science Foundation of Shaanxi Province.

Source: https://pubmed.ncbi.nlm.nih.gov/38430256/ 

Bian, Z., Wu, X., Chen, Q. et al. (2024). “Oct4 activates IL-17A to orchestrate M2 macrophage polarization and cervical cancer metastasis.” Cancer Immunol Immunother 73, 73 (2024). https://doi.org/10.1007/s00262-023-03596-z.

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