Abstract
Purpose: :
There is increasing evidence that cancer can arise from a cancer stem cell (CSC), a tumor–initiating cell that has properties similar to those of stem cells. CSCs have been identified in a variety of malignancies, including those of blood, brain and breast. Here, we test whether stem cell–like populations exist in uveal melanoma (UM).
Methods: :
Normal uveal melanocytes, UM tumors, as well as UM cell lines were examined for the presence of stem cell markers by semi–quantitative RT–PCR and immunofluorescence. In addition, Hoechst dye exclusion, mediated by the stem cell surface marker ATP–binding cassette transporter G2 subfamily (ABCG2), was assessed by flow cytometry in normal uveal melanocytes and UM cell lines.
Results: :
Normal uveal melanocytes, UM tumors and UM cell lines express the following stem cell markers : nestin, p63, aldehyde dehydrogenase 1 (ALDH1), ABCG2, stem cell factor (SCF), musashi, SRY–related HMG–box gene 2 (SOX–2) and nucleostemin. Flow cytometric analyses confirmed the presence of small subpopulations of cells excluding Hoechst dye in normal uveal melanocytes and UM cell lines, consistent with the presence of the calcium–sensitive ABCG2 protein.
Conclusions: :
UM cells contain a small subpopulation of cells that exhibit a CSC–like phenotype. Further studies are necessary to confirm self–renewal and chemoresistant properties of these cells. The existence of even a small subpopulation of chemoresistant CSCs in UM would have a significant impact on future treatments.
Keywords: melanoma • melanocytes • gene/expression