title: A tumorigenic subpopulation with stem cell properties in melanomas.
abstract: 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 approximately 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.
authors.affiliation: Program of Molecular and Cellular Oncogenesis, The Wistar Institute and Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, PA 19104, USA.
authors.forename: Dong
authors.initials: D
authors.lastname: Fang
authors.forename: Thiennga K
authors.initials: TK
authors.lastname: Nguyen
authors.forename: Kim
authors.initials: K
authors.lastname: Leishear
authors.forename: Rena
authors.initials: R
authors.lastname: Finko
authors.forename: Angela N
authors.initials: AN
authors.lastname: Kulp
authors.forename: Susan
authors.initials: S
authors.lastname: Hotz
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Van Belle
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Xu
authors.forename: David E
authors.initials: DE
authors.lastname: Elder
authors.forename: Meenhard
authors.initials: M
authors.lastname: Herlyn
mesh_terms: D000818:Animals; D018951:Antigens, CD20 / Q000096:biosynthesis; D002448:Cell Adhesion; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D005347:Fibroblasts / Q000166:cytology; D005434:Flow Cytometry; D006801:Humans; D008545:Melanoma / Q000473:pathology*; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000473:pathology*; D018874:Spheroids, Cellular; D014183:Transplantation, Heterologous
chemical_list: D018951:Antigens, CD20