Identification of stem cell like population in human melanoma

The cancer stem cell (CSC) hypothesis suggests that neoplastic clones are maintained exclusively by a rare fraction of cells with stem cell proprieties. Although the existence of CSCs in several tumors, no evidences for CSCs exist in melanoma at yet. Herein, we show, for the first time, that melanoma contains CSCs expressing typical markers and gene expected for stem cells both in vitro and in vivo. In vitro, two melanoma cell lines (WM115 and A375) co-expressed together with neuronal, endothelial and lymphatic markers, CD133 and CXCR4 (95-98%). In fresh isolated biopsy CD133 is expressed by a limited percentage of cells (about 1%) while CXCR4 is expressed by all the cells (95-98%). Furthermore, in addition to CD133, both melanoma cell lines show a growth similar to normal human stem cells, forming spheres and expressing mature neural markers such as -tubulin type III and microtubule-associated protein 2 (MAP2) as well as immature and mature oligodendrocyte markers such as A2B5 and GalC. The phenotypic similarities between normal neuronal stem cell and CSCs found in melanoma cell lines, was also confirmed by the analysis of extra-neural markers. In fact, both cell lines express several immature and mature endothelial markers such as VE-cadherin, VEGF, Flk-1, Ang 1 and 2, Tie 2, CD31, ephrine A2, endogline, semaphorine 3A, neuropilin 1, Notch and N-cadherin. Interestingly, the acquisition of the lymphatic markers seems to correlate with melanoma progression, possibly facilitating the metastatic dissemination of melanoma cells.