Cited by 1,280Cancer Cells and MetastasisMesenchymal stem cell researchCutaneous Melanoma Detection and Management

A tumorigenic subpopulation with stem cell properties in melanomas

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Fang, Dong, Nguyen, Thiennga K., Leishear, Kim, Finko, Rena, Kulp, Angela N., Hotz, Susan, Van Belle, Patricia A., Xu, Xiaowei +2 more·2005·Cancer Research

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.

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  1. Jiang Y, Jahagirdar BN, Reinhardt RL, et al. Pluri- potency of mesenchymal stem cells derived from adult marrow. Nature 2002;418:41-9.

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Authors
Fang, D., Nguyen, T. K., Leishear, K., Finko, R., Kulp, A. N., Hotz, S., Van Belle, P. A., Xu, X., Elder, D. E., & Herlyn, M.
Affiliations
  • The Wistar Institute (US)
  • University of Pennsylvania (US)
  • 2Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
Venue
Cancer Research
Published
2005-10-15
Volume
65
Issue
20
Pages
9328-9337
ISSN
  • 0008-5472 (ISSN-L)
  • 1538-7445
OpenAlex
W2072569544
Cited by
1,280
References
60
Citations by year
2026: 6 · 2025: 10 · 2024: 25 · 2023: 41 · 2022: 42 · 2021: 31 · 2020: 48 · 2019: 52 · 2018: 40 · 2017: 74 · 2016: 61 · 2015: 91 · 2014: 76 · 2013: 90 · 2012: 123
FWCI
28.14
Type
journal article
Language
en
Open access
Locations
  • Cancer Research (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Pennsylvania Department of Health
  • National Institutes of Health (CA 10815, CA-25874)
  • National Cancer Institute (R01CA080999, CA-10815, CA 76674, CA-25874, R01CA076674, CA80999, P01CA025874, P30CA010815)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Health Sciences › Medicine › Oncology › Cutaneous Melanoma Detection and Management
Keywords
melanoma, cancer stem cells, metastatic melanoma, spheroid cells, multipotent differentiation, self-renewal, tumorigenicity, CD20, tumor heterogeneity, serial transplantation, melanoma cell lines
MeSH terms
Animals, Cell Adhesion, Cell Differentiation, Fibroblasts, Flow Cytometry, Humans, Melanoma, Neoplasm Transplantation, Transplantation, Heterologous, Neoplastic Stem Cells, Mice, SCID, Spheroids, Cellular, Antigens, CD20, Cell Line, Tumor, Mice

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