In addition to its well-established immunosuppressive actions,
tryptophan 2,3-dioxygenase (TDO) appears to elicit direct effects on
tumor cell function. Although TDO has been associated with
cancer stemness, its involvement in
melanoma stem cell biology remains largely unknown. Since we showed that by upregulating TDO,
dexamethasone (dex) promotes proliferation and migration of SK-Mel-28 human
melanoma cells, we sought to investigate dex effects on
melanoma spherogenesis and stemness, and whether these events are mediated by TDO. We demonstrate here that dex significantly upregulates TDO in A375, a more aggressive
melanoma cell line, confirming that dex effects are not limited to SK-Mel-28 cells. Moreover, dex stimulates spherogenesis of both cell lines, which is mediated by TDO, evident by its suppression with
680C91, a TDO inhibitor. The formed melanospheres appear to be enriched with embryonic stem cell marker mRNAs, the expression of which is potentiated by dex. Expression of cancer stem cell markers (CD133, CD44,
ganglioside GD2) was significantly increased in A375 spheres, as detected by flow cytometry. Taken together, our results suggest that TDO could represent a promising target in the management of
melanoma and that dex, routinely used as a co-medication also in advanced
melanoma, may stimulate
melanoma cell function/
tumor-supporting properties, a rather debilitating and undesired side effect.