Some cancers are thought to follow a cancer stem cell (CSC) model in which unidirectional, hierarchical relationships exist between tumorigenic and non-tumorigenic cells within tumours, based on irreversible epigenetic changes that occur in some progeny of tumorigenic cells, rendering them phenotypically distinct and incapable of tumour formation.
In melanoma, conflicting evidence questions whether a CSC model applies in which tumorigenic CD271+ cells self-renew and hierarchically beget less/non-tumorigenic CD271- cells [1-3]. However, comparisons of published studies [1-3] are confounded by assays undertaken by different investigators, using different methods and different melanomas. We thus sought to determine if differences in published assays impact the different interpretations of these studies.
Melanomas (n=20) were divided and dissociated side-by-side according to different published assays. Yields of viable melanoma cells were similar between assays. Dissociated cells were separated by flow cytometry according to CD271 expression. Among all melanomas tested, the percentages of CD271+ cells varied widely (0-91%) and no significant differences in CD271 expression patterns were identified according to tumour dissociation method.
CD271- and CD271+ cells isolated using different methods were transplanted in NOD/SCIDIl2gr-/-(NSG) mice to test additional variations in tumorigenesis conditions (NSG recipient gender, matrigel type). Consistent tumour formation was observed from CD271- and CD271+ cells irrespective of dissociation or tumorigenesis conditions. Expression of CD271 in tumours derived from both cell phenotypes varied widely, even in tumours derived from the same number of phenotypically identical cells from the same melanoma.
We thus found that published differences regarding whether melanoma follows a CD271-based CSC model do not relate to assay differences between studies. Rather, intrinsic instability of melanoma cells contributes to variable expression of markers in melanoma. Our observations indicate that melanoma research and treatment are unlikely to be advanced by application of the CSC model.