Fig. 1

Phenotypical heterogeneity of melanoma cells in vitro. a Immunofluorescence microscopy (IF) of melanoma cells revealed only a small number of cells positive for the stage-specific embryonic antigens (SSEA) 4 and 5; as well as slow-cycling cells which retain the lipophilic dye PKH26 (red). Cells with active WNT-signaling, driving expression of a LEF/TCF1-controlled GFP, or cells positive for either CD44 or tropomyosin-related kinases (TRKs) were infrequently observed as well. More frequently observed was the expression of CD271, HMGA2, FGF13, SOX10 (ubiquitous), SOX2, or CSPG4. Cultures of melanoma cells exhibiting co-existing, interconnected phenotypes as shown for CD271 and CD133 are rare. b Intratumor heterogeneity, shown by IF of tumors for CD271 (green) and either vimentin, CD133, MART1 or SSEA5 (all red). In (a) and (b), DAPI served as a nuclear dye. Scale bars indicate 50 μm. c Schematic representation of the regional distribution of melanoma brain metastases (BM), numbers represent the frequency of BM observed in 115 patients