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 f20% 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. (Cancer Res 2005; 65(20): 9328-37)

Beyond tumorigenesis: cancer stem cells in metastasis

“…Similar to normal stem cells, CSCs can reproduce themselves through the process of self-renewal, which can be studied in serial transplantation assays. Additionally, cancers derived from purified CSCs recapitulate the heterogeneous phenotypes of the parental cancer from [32,47] (ii) c-Kit + Thy1 low Sca1 + Lin - [134,135] Breast (ii) CD24 med CD49f hi [6] (i) CD44 + CD24 -/low ESA + Lin - [33] (ii) CD29 hi CD24 + Lin - [7] Brain (i) CD133 + Lin - [41] (i) CD133 + [34][35][36] Lung (ii) Sca-1 + CD34 + Lin - [5] (ii) Sca-1 + CD34 + Lin - [5] Skin (ii) CD34 + CD71 low α6-integrin high [136] (i) CD20 + [137] Prostate (i) CD133 + a2b1 hi [138] (i) CD44 + α2β1 hi CD133 + [139] www.cell-research.com | Cell Research Feng Li et al npg which they were derived, reflecting the differentiation capacity of CSCs [32,33]. These observations suggest that CSCs contain the complete genetic programs necessary to initiate and sustain tumor growth.…”

A ubiquitin ligase, skeletrophin, is a negative regulator of melanoma invasion

“…The Notch pathway mediates tissue differentiations and homeostasis by controlling stem cells. Interestingly, recent studies indicated that melanoma contains a subpopulation of tumor stem cells that can differentiate into multiple cell lineages and contribute to tumor progression (Fang et al, 2005;Grichnik et al, 2006). It is likely that aberrant Notch pathway participated in the tumorigenesis of melanoma by regulating tumor stem cells.…”

CD44+CD24− prostate cells are early cancer progenitor/stem cells that provide a model for patients with poor prognosis

“…It is thought that the cancer stem cells survive conventional treatment to later re-emerge more resistant to therapy (Reya et al, 2001). To date, putative cancer stem cells have been identified in blood (Bonnet and Dick, 1997), brain (Singh et al, 2004), breast (Al-Hajj et al, 2003), lung (Kim et al, 2005), skin (Fang et al, 2005), pancreas (Li et al, 2007), colon (O'Brien et al, 2007;Ricci-Vitiani et al, 2007), and prostate (Collins et al, 2005;Patrawala et al, 2006).…”