Increased cytokine secretion in head and neck cancer upon p38 mitogen-activated protein kinase activation
Christine Riebe1, Ralph Pries, Andrea Kemkers
1Department of Otorhinolaryngology, University of Schleswig-Holstein Campus Lübeck, 23538 Lübeck, Germany.
Abstract:
Head and neck squamous cell carcinoma (HNSCC) is one of the most frequently diagnosed cancers. It is believed that tumor production of various immune suppressive mediators contributes to massively impaired immune functions, but the underlying signal transduction pathways are mostly unknown. Phosphorylation levels of MAP (mitogen-activated protein) kinase p38 were analyzed in permanent cell lines as well as in solid tumor tissue of HNSCC using flow cytometry and SDS-PAGE. Cytokine secretion was determined using the Cytometric Bead Array Flex Set system. MAP kinase p38 was shown to be activated in HNSCC by phorbol 12-myristate 13-acetate. Activation of p38 led to decreased cell proliferation and increased secretion of cytokines IL-6 and IL-8 in HNSCC. Our data provide novel insights into the origin of the HNSCC microenvironment. A better understanding of these molecular mechanisms in HNSCC is essential for novel drug development and improvement of the clinical perspective of this tumor type.
Insights
Head and neck squamous cell carcinoma (HNSCC) involves impaired immune function. This study shows that activating MAP (mitogen-activated protein) kinase p38 in HNSCC decreases cell proliferation and increases IL-6 and IL-8 cytokine secretion.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Head and neck squamous cell carcinoma (HNSCC) is a prevalent cancer associated with suppressed immune functions.
- The specific signal transduction pathways driving immune suppression in HNSCC remain largely unidentified.
Purpose of the Study:
- To investigate the role of MAP (mitogen-activated protein) kinase p38 signaling in HNSCC.
- To elucidate the impact of p38 activation on HNSCC cell behavior and cytokine secretion.
Main Methods:
- Analysis of MAP kinase p38 phosphorylation levels in HNSCC cell lines and tumor tissues via flow cytometry and SDS-PAGE.
- Quantification of cytokine secretion (IL-6, IL-8) using the Cytometric Bead Array Flex Set system.
- Induction of p38 activation using phorbol 12-myristate 13-acetate.
Main Results:
- MAP kinase p38 was activated in HNSCC models.
- p38 activation led to reduced HNSCC cell proliferation.
- Increased secretion of cytokines IL-6 and IL-8 was observed following p38 activation.
Conclusions:
- MAP kinase p38 signaling plays a significant role in modulating the HNSCC microenvironment.
- Understanding these molecular mechanisms offers potential for new therapeutic strategies and improved clinical outcomes for HNSCC patients.
Related Concept Videos
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
MAPK Signaling Cascades
Mitogens and the Cell Cycle
The JAK-STAT Signaling Pathway
NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
