Promotion effects of mono-2-ethyhexyl phthalate (MEHP) on migration and invasion of human melanoma cells via activation of TGF-β signals.

Malignant melanoma is one of the most leading forms of skin cancer associated with a low patient survival rate. There is an urgent need to illustrate risk factors that can trigger the motility of melanoma cancer cells. Our present study revealed that mono-(2-ethylhexyl)phthalate (MEHP) exposure can significantly increase the in vitro migration and invasion of WM983A and A375 cells. Among the tested cytokines, MEHP can increase the expression of transforming growth factor β (TGF-β). Inhibition of TGF-β via its neutralization antibody can attenuate MEHP-induced cell migration and invasion. Further, upregulation of TGF-β mediated MEHP-induced activation of Smad signals and upregulation of Snail in melanoma cells. Blocking the TGF-β/Smad signal pathway can attenuate MEHP-induced cell migration. Estrogen receptor α (ERα) was essential for MEHP-induced expression of TGF-β. In addition, MEHP can increase the expression of ERα in melanoma cells. Collectively, our study found that MEHP can stimulate the progression of melanoma via TGF-β signals. SIGNIFICANCE: Mono-(2-ethylhexyl)phthalate (MEHP) is the active and most toxic metabolite of di(2-ethylhexyl)phthalate (DEHP). Our present study revealed that MEHP can trigger the in vitro migration and invasion of melanoma cells via upregulation of TGF-β/Snail signals. It revealed that daily exposure to MEHP might be a risk factor for melanoma patients.