SOX2 is an embryonic neural crest stem-cell
transcription factor recently shown to be expressed in human
melanoma and to correlate with experimental
tumor growth. SOX2 binds to an enhancer region of the gene that encodes for
nestin, also a neural progenitor cell
biomarker. To define further the potential relationship between SOX2 and
nestin, we examined co-expression patterns in 135
melanomas and 37
melanocytic nevi. Immunohistochemical staining in 27
melanoma tissue sections showed an association between SOX2 positivity, spindle cell shape and a peripheral
nestin distribution pattern. In contrast, SOX2-negative cells were predominantly epithelioid, and exhibited a cytoplasmic pattern for
nestin. In tissue microarrays, co-expression correlated with
tumor progression, with only 11% of
nevi co-expressing SOX2 and
nestin in contrast to 65% of metastatic
melanomas, and preliminarily, with clinical outcome. Human
melanoma lines that differentially expressed constitutive SOX2 revealed a positive correlation between SOX2 and
nestin expression.
Experimental melanomas grown from these respective cell lines in murine subcutis and dermis of xenografted human skin maintained the association between SOX2-positivity, spindle cell shape, and peripheral
nestin distribution. Moreover, the cytoplasmic pattern of
nestin distribution was observed in xenografts generated from SOX2-knockdown A2058
melanoma cells, in contrast to the peripheral
nestin pattern seen in
tumors grown from A2058 control cells transfected with non-target
shRNA. In aggregate, these data further support a biologically significant linkage between SOX2 and
nestin expression in human
melanoma.