Cancer stem cells and human malignant melanoma

Pigment Cell Melanoma Res. 2008 Feb;21(1):39-55. doi: 10.1111/j.1755-148X.2007.00427.x.

Abstract

Cancer stem cells (CSC) have been identified in hematological malignancies and several solid cancers. Similar to physiological stem cells, CSC are capable of self-renewal and differentiation and have the potential for indefinite proliferation, a function through which they may cause tumor growth. Although conventional anti-cancer treatments might eradicate most malignant cells in a tumor, they are potentially ineffective against chemoresistant CSC, which may ultimately be responsible for recurrence and progression. Human malignant melanoma is a highly aggressive and drug-resistant cancer. Detection of tumor heterogeneity, undifferentiated molecular signatures, and increased tumorigenicity of melanoma subsets with embryonic-like differentiation plasticity strongly suggest the presence and involvement of malignant melanoma stem cells (MMSC) in the initiation and propagation of this malignancy. Here, we review these findings in the context of functional properties ascribed to melanocyte stem cells and CSC in other cancers. We discuss the association of deregulated signaling pathways, genomic instability, and vasculogenic mimicry phenomena observed in melanoma subpopulations in light of the CSC concept. We propose that a subset of MMSC may be responsible for melanoma therapy-resistance, tumor invasiveness, and neoplastic progression and that targeted abrogation of a MMSC compartment could therefore ultimately lead to stable remissions and perhaps cures of metastatic melanoma.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Adult Stem Cells / pathology
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Cell Differentiation
  • Cell Lineage
  • Cell Proliferation
  • Cell Transformation, Neoplastic / drug effects
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology*
  • Drug Resistance, Neoplasm
  • Gene Expression Regulation, Neoplastic
  • Genomic Instability
  • Humans
  • Melanocytes / drug effects
  • Melanocytes / metabolism
  • Melanocytes / pathology*
  • Melanoma / drug therapy
  • Melanoma / epidemiology
  • Melanoma / genetics
  • Melanoma / metabolism
  • Melanoma / pathology*
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology*
  • Signal Transduction* / drug effects
  • Signal Transduction* / genetics

Substances

  • Antineoplastic Agents