IADR Abstract Archives
Regulation of Calprotectin by the Aryl Hydrocarbon Receptor in HNSCC
Objectives: Head and neck squamous cell carcinoma (HNSCC) is a devastating disease with poor outcomes. We have reported that calprotectin (S100A8/A9) is a likely tumor suppressor in HNSCC. The aryl hydrocarbon receptor (AHR) appears to respond to carcinogens implicated in HNSCC initiation. We are testing the hypothesis that AHR activation by HNSCC carcinogens downregulates S100A8/A9 in HNSCC, potentially dampening native tumor suppression.
Methods: Buccal-carcinoma-derived TR146 wild-type (WT) cells were treated with AHR ligands: benzo[a]pyrene (BaP), a tobacco carcinogen, and 4-nitroquinoline N-oxide (4-NQO), a mutational surrogate. Changes in AHR activity (CYP1B1) and S100A8/A9 expression were assessed by RT-qPCR. To further investigate AHR's role, we have established a Cas9-stable TR146 cell line and are in the process of generating AHR-knockout cells using CRISPR technology.
Results: BaP activated AHR and exhibited a weak bimodal effect on S100A8/A9 expression in TR146 WT cells. In these cells, 4-NQO also activated AHR in a dose-dependent manner. The impact of AHR knockout on the response of S100A8/A9 to BaP and 4-NQO is currently being investigated.
Conclusions: AHR activation by HNSCC carcinogens BaP and 4-NQO has been demonstrated in TR146 cells. The AHR appears to respond to carcinogens by down-regulating S100A8/A9 mRNA. Ongoing studies with AHR-knockout cancer cells are expected to provide crucial insights into this relationship.
Methods: Buccal-carcinoma-derived TR146 wild-type (WT) cells were treated with AHR ligands: benzo[a]pyrene (BaP), a tobacco carcinogen, and 4-nitroquinoline N-oxide (4-NQO), a mutational surrogate. Changes in AHR activity (CYP1B1) and S100A8/A9 expression were assessed by RT-qPCR. To further investigate AHR's role, we have established a Cas9-stable TR146 cell line and are in the process of generating AHR-knockout cells using CRISPR technology.
Results: BaP activated AHR and exhibited a weak bimodal effect on S100A8/A9 expression in TR146 WT cells. In these cells, 4-NQO also activated AHR in a dose-dependent manner. The impact of AHR knockout on the response of S100A8/A9 to BaP and 4-NQO is currently being investigated.
Conclusions: AHR activation by HNSCC carcinogens BaP and 4-NQO has been demonstrated in TR146 cells. The AHR appears to respond to carcinogens by down-regulating S100A8/A9 mRNA. Ongoing studies with AHR-knockout cancer cells are expected to provide crucial insights into this relationship.