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Interleukin-6 as a therapy target in oral squamous carcinoma
1Experimental Urology, Department of Urology, Anichstrasse 35, A-6020 Innsbruck, Austria. zoran.culig@i-med.ac.at
Introduction:
Interleukin-6 (IL-6) is a multifunctional cytokine which is implicated in the regulation of immune responses and cellular events. It may activate signaling pathways of Janus kinase/signal transducer and activator of transcription (JAK/STAT) factors, mitogen-activated protein kinases, and Akt. IL-6 could exert pleiotropic effects in a variety of cancers.
Areas Covered:
Oral squamous cell carcinoma epidemiology, pathology, regulation by IL-6, and experimental therapy.
Expert Opinion:
Oral squamous cell carcinoma development is in part facilitated by chronic epithelial irritations and this tumor is more frequent in smokers or individuals who consume excessive amounts of alcohol. IL-6 levels are elevated in this neoplasm and IL-6 is considered a bad prognostic factor in oral cancer. IL-6 secretion in oral squamous cancer is facilitated by the microenvironment, in particular by stromal derived factor-1. IL-6 function in non-malignant and malignant diseases is controlled by endogenous inhibitors of cytokine signaling. IL-6 action in oral squamous cancer is largely mediated by the JAK/STAT3 pathway and may lead to epithelial to mesenchymal transition, thus contributing to tumor progression. IL-6 also enhances angiogenesis and lymphangiogenesis through regulation of vascular endothelial growth factor. In addition, experimental anti-IL-6/anti-IL-6 receptor-targeted therapies in oral cancer have been proposed.
Insights
Interleukin-6 (IL-6) is elevated in oral squamous cell carcinoma, promoting tumor progression via pathways like JAK/STAT3. Targeting IL-6 offers potential new therapies for this cancer.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Interleukin-6 (IL-6) is a cytokine involved in immune regulation and cellular events.
- IL-6 signaling pathways include Janus kinase/signal transducer and activator of transcription (JAK/STAT), mitogen-activated protein kinases, and Akt.
- IL-6 has diverse roles in various cancers.
Purpose of the Study:
- To review the epidemiology, pathology, and IL-6 regulation of oral squamous cell carcinoma (OSCC).
- To discuss the role of IL-6 in OSCC development and progression.
- To explore experimental therapies targeting IL-6 in OSCC.
Main Methods:
- Literature review of OSCC epidemiology and pathology.
- Analysis of IL-6's role in OSCC pathogenesis.
- Examination of experimental anti-IL-6 therapies for OSCC.
Main Results:
- IL-6 levels are elevated in OSCC and are a negative prognostic factor.
- IL-6 promotes OSCC progression through pathways like JAK/STAT3, leading to epithelial-mesenchymal transition.
- IL-6 enhances angiogenesis and lymphangiogenesis by regulating vascular endothelial growth factor.
Conclusions:
- Chronic irritation, smoking, and alcohol contribute to OSCC development.
- The tumor microenvironment, including stromal derived factor-1, facilitates IL-6 secretion in OSCC.
- IL-6 action in OSCC is largely mediated by JAK/STAT3, driving tumor progression, angiogenesis, and lymphangiogenesis.
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