Aryl Hydrocarbon Receptor Mediates Cell Proliferation Enhanced by Benzo[a]pyrene in Human Lung Cancer 3D Spheroids

Development of Human Lung Induction Models for Air Pollutants’ Toxicity Assessment

“…However, a few studies have reported toxicity evaluations with cell line-based lung organoids. 50,51 For example, Kabadi et al tested several carbon nanomaterials with 3D organoids consisting of BEAS-2B epithelial cells, macrophages, and fibroblasts and validated the novelty of the model. 50 In our case, instead of differentiating hLPs in monolayer, we collected the cells, embedded them in Matrigel, and kept the culture in dome conditions for organoid formation (Figure 5A).…”

“…Organoid-based induction protocols and 3D culture systems have not been popularly used in the toxicology field. However, a few studies have reported toxicity evaluations with cell line-based lung organoids. , For example, Kabadi et al tested several carbon nanomaterials with 3D organoids consisting of BEAS-2B epithelial cells, macrophages, and fibroblasts and validated the novelty of the model …”

Regulation of long non-coding RNA expression by aryl hydrocarbon receptor activation

“…It should be noted that activation of the AhR by its endogenous ligand ITE has inhibitory effects on proliferation and migration of HCC cells [385]. Thus, different AhR ligands can have very distinctive and often divergent outcomes [33,212,225,386,387] antisense RNA 1 (RASAL2-AS1), long intergenic non-protein coding RNA 2532 (LINC02532), and FP671120.5. Three of the DE lncRNAs (FP236383.1, HSD17B7P2, and AL049840.2) have been identified as DEGs several human diseases [394][395][396].…”

“…Numerous studies have investigated AhR expression and activation in regulating cell survival and proliferation [386,387,397] and some have shown that the AhR promotes cell survival and proliferation through a ligand-independent mechanism [397], whereby overexpression of the AhR was sufficient to stimulate proliferation of A549 cells [398]. Even in the absence of ligand, AhR in the NSCLC cell lines have been linked to alterations in cell function.…”

“…For example, H1299 cells have higher invasion compared to A549 cells due to the cellular level of AhR, which is lower in H1299 cells than in A549 cells [397]. However, AhR activation also has effects on proliferation that are dependent on both the cell and ligand type [386,387]. For example, in various NSCLC and HCC cell lines, AhR activation by TCDD promotes cell survival, proliferation, migration, and invasion via the activation AKT serine/threonine kinase (Akt) pathway.…”