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[Cancer Research 65, 9328-9337, October 15, 2005]
© 2005 American Association for Cancer Research

Cell and Tumor Biology

A Tumorigenic Subpopulation with Stem Cell Properties in Melanomas

Dong Fang1, Thiennga K. Nguyen1, Kim Leishear1, Rena Finko1, Angela N. Kulp1, Susan Hotz2, Patricia A. Van Belle2, Xiaowei Xu2, David E. Elder2 and Meenhard Herlyn1

1 Program of Molecular and Cellular Oncogenesis, The Wistar Institute and 2 Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania

Requests for reprints: Meenhard Herlyn, The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104. Phone: 215-898-3950; Fax: 215-898-0980; E-mail: parsons{at}wistar.org.

Recent studies suggest 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 several malignancies, including those of blood, brain, and breast. Here, we test whether stem cell–like populations exist in human melanomas. In ~20% of the metastatic melanomas cultured in growth medium suitable for human embryonic stem cells, we found a subpopulation of cells propagating as nonadherent spheres, whereas in standard medium, adherent monolayer cultures were established. Individual cells from melanoma spheres (melanoma spheroid cells) could differentiate under appropriate conditions into multiple cell lineages, such as melanocytic, adipocytic, osteocytic, and chondrocytic lineages, which recapitulates the plasticity of neural crest stem cells. Multipotent melanoma spheroid cells persisted after serial cloning in vitro and transplantation in vivo, indicating their ability to self-renew. Furthermore, they were more tumorigenic than adherent cells when grafted to mice. We identified similar multipotent spheroid cells in melanoma cell lines and found that the stem cell population was enriched in a CD20+ fraction of melanoma cells. Based on these findings, we propose that melanomas can contain a subpopulation of stem cells that contribute to heterogeneity and tumorigenesis. Targeting this population may lead to effective treatments for melanomas.




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