Schatton Tobias, Frank Markus H
Transplantation Research Center, Children's Hospital Boston & Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Pigment Cell Melanoma Res. 2008 Feb;21(1):39-55. doi: 10.1111/j.1755-148X.2007.00427.x.
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.
癌症干细胞（CSC）已在血液系统恶性肿瘤和多种实体癌中被鉴定出来。与生理干细胞相似，癌症干细胞能够自我更新和分化，并具有无限增殖的潜力，它们可能通过这种功能导致肿瘤生长。尽管传统的抗癌治疗可能会根除肿瘤中的大多数恶性细胞，但它们对化疗耐药的癌症干细胞可能无效，而这些干细胞最终可能是复发和进展的原因。人类恶性黑色素瘤是一种极具侵袭性和耐药性的癌症。肿瘤异质性、未分化分子特征的检测，以及具有胚胎样分化可塑性的黑色素瘤亚群的肿瘤发生能力增加，强烈提示恶性黑色素瘤干细胞（MMSC）在这种恶性肿瘤的起始和传播中存在并发挥作用。在此，我们结合赋予黑素细胞干细胞和其他癌症中癌症干细胞的功能特性来综述这些发现。我们根据癌症干细胞的概念，讨论在黑色素瘤亚群中观察到的信号通路失调、基因组不稳定和血管生成拟态现象之间的关联。我们提出，一部分MMSC可能是黑色素瘤治疗耐药、肿瘤侵袭性和肿瘤进展的原因，因此，靶向消除MMSC区室最终可能导致转移性黑色素瘤的稳定缓解甚至治愈。
