Increased, Proliferation (Endothelial cells) leads to Increased, Angiogenesis

The activation of the AhR can lead to an increased endothelial cell migration. This was found when HMEC-1 or EA.hy926 cells were co-cultured with ER-positive MCF-7 cells and triple negative MDA-MB-231 cells (Pontillo et al., 2015 Nov 19, Zárate et al., 2020 Aug). The assay mainly used was the Matrigel® / tube formation assay. Only one study found an increase in endothelial cell proliferation and not migration, therefore it was not kept as a KE (Pontillo et al., 2015 Nov 19). The main pathway explaining this relationship was again related to the activation of COX2 and subsequently to the increase in VEGF. The association between the activation of the AhR and endothelial cell migration was classified as “weak” since only 2 studies explored this feature, and both used hexachlorobenzene as a stressor. However, these works were robust with strong evidence, and both found a reversed association after AhR blockage. No contradicting results were found in the scientific literature.

As opposed to our work, another AOP displayed a link between AhR activation and angiogenesis (AOP 150) and found that activation of the receptor could decrease VEGF production with moderate evidence and quantitative understanding. It must be noted that these AOPs applied only to chicken, zebrafish, and certain rodents whereas our AOP concerns humans. As detailed further, the AhR presents a variability between species which must be considered.