Shi Guang Song
Song, Shi Guang
Faculty / Advisor: Ali, Hydar
University of Pennsylvania School of Dental Medicine, Department of Basic and Translational Sciences
Oral squamous cell carcinoma is one of the most common cancers in the world and has shown modest improvements in prognosis over the past decade. An increase in mast cell density is associated with angiogenesis and worsened prognosis of many cancers. This study seeks to review how mast cell-released mediators can affect oral squamous carcinoma development and prognosis.Methods
The keywords “mast cells and oral squamous cell carcinoma” and “mast cells and oral cancer” were used in PubMed through the University of Pennsylvania Scool of Dentistry Library Database. Subheadings included "Mouth Neoplasms"[Mesh] AND "Mast Cells"[Mesh].Results
An increase in mast cell activation in tissue areas close to the tumor was found, along with the release of more histamine, tryptase, and chymase. An increase in expression of two types of histamine receptors was also found, while the expression of the H4 receptor, which functions to modulate tumor development, was decreased. The cathelicidin LL-37 and the epithelial cell-derived antimicrobial peptide human β-defensin-2 activate mast cells through G-protein coupled receptor MRGPRX2. MRGPRX2 activation leads to further degranulation and release of proinflammatory mediators.Conclusion
The roles of mast cells in squamous cell carcinoma are multifaceted and further investigation is needed. The release of histamine, tryptase, and chymase suggests altered signaling pathways involving mast cells in carcinoma progression. In oral squamous cell carcinoma, human β-defensin-2 is upregulated, leading to increased MRGPRX2 activation while LL-37, a tumor suppressor in this cancer, is downregulated. Increased MRGPRX2 activation can potentially increase oral cancer progression and worsen prognosis as its activation through mediators such as human β-defensin and LL-37 results in MC degranulation. MRGPRX2 could play a role in creating a pro-tumorigenic environment, angiogenesis, and malignant cell proliferation. Further study into the roles of these mediators can potentially present targets for future treatment.