IADR Abstract Archives
The Interplay Between Aryl Hydrocarbon Receptor and Calprotectin in HNSCC
Objectives: Head and neck squamous cell carcinoma (HNSCC) is a debilitating disease with low 5-year survival rates and poor functional outcomes in more than 40% of patients after treatment. Known causative HNSCC agents appear to engage the aryl hydrocarbon receptor (AHR), which yields a transcription factor implicated in the initiation of HNSCC. With decreasing levels in HNSCC tumors, calprotectin (S100A8/A9) appears to function as a tumor suppressor in these cancers. We seek to learn whether AHR activation reduces the expression of S100A8/A9, dampening native HNSCC suppression.
Methods: To assess AHR activation that may be relevant to HNSCC, we designed an in-vitro system in which buccal-carcinoma-derived cell lines were cultured and treated with diverse ligands: 6-formylindolo[3,2-b] carbazole (FICZ), a positive activator; 4-nitroquinoline N-oxide (4-NQO), a mutational surrogate of tobacco smoke; microbial metabolites of Porphyromonas gingivalis; and CH223191, a ligand selective antagonist of the AHR. Changes in AHR-dependent gene expression, including AHR, CYP1B1, and S100A8/A9, were determined using RT-qPCR.
Results: We showed that genetic expression of CYP1B1 (which marks AHR activity) increased following treatment with these ligands and decreased following treatment with CH223191. The relationship between AHR and S100A8/A9 is currently inconclusive.
Conclusions: The transcriptional response of AHR following ligand activation may be ligand-dependent. For example, the anticipated downregulation of S100A8/A9 genes may depend on the AHR-activating agent.
Methods: To assess AHR activation that may be relevant to HNSCC, we designed an in-vitro system in which buccal-carcinoma-derived cell lines were cultured and treated with diverse ligands: 6-formylindolo[3,2-b] carbazole (FICZ), a positive activator; 4-nitroquinoline N-oxide (4-NQO), a mutational surrogate of tobacco smoke; microbial metabolites of Porphyromonas gingivalis; and CH223191, a ligand selective antagonist of the AHR. Changes in AHR-dependent gene expression, including AHR, CYP1B1, and S100A8/A9, were determined using RT-qPCR.
Results: We showed that genetic expression of CYP1B1 (which marks AHR activity) increased following treatment with these ligands and decreased following treatment with CH223191. The relationship between AHR and S100A8/A9 is currently inconclusive.
Conclusions: The transcriptional response of AHR following ligand activation may be ligand-dependent. For example, the anticipated downregulation of S100A8/A9 genes may depend on the AHR-activating agent.