Okamoto Oswaldo Keith
Departamento de Neurologia e Neurocirurgia, Disciplina de Neurologia Experimental, Escola Paulista de Medicina/Universidade Federal de São Paulo, Brazil.
Expert Rev Mol Diagn. 2009 Sep;9(6):545-54. doi: 10.1586/erm.09.40.
Biologically distinct populations of neoplastic stem cells have been identified in a variety of human cancers, in which they are associated with the initial steps of tumorigenesis. The intrinsic properties of self-renewal, clonogenicity and multipotency, along with a longer half-life within the body, may render normal adult stem cells more prone to accumulate genetic mutations leading to neoplastic transformation, as predicted by the cancer stem cell hypothesis. Tumor formation is also associated with the pluripotency of embryonic stem cells and may be induced as a consequence of complete dedifferentiation of mature cells, as recently reported for induced pluripotent stem cells. The tumor-initiating cell phenotype may result from genetic alterations affecting the expression of critical genes regulating typical stem cell processes such as self-renewal and pluripotency, in addition to genes determining stem cell senescence or longevity. Detailed genome-wide analysis of cancer stem cells and respective normal counterparts will help elucidate the cellular and molecular nature of tumors, providing fundamental information about the initial steps toward malignant transformation. Devising ways of detecting such genetic and epigenetic alterations and cell populations displaying them would allow medical interventions at the early phases of cancer development, thereby improving the chances of favorable clinical outcomes.
在多种人类癌症中已鉴定出生物学上不同的肿瘤干细胞群体，它们与肿瘤发生的起始步骤相关。自我更新、克隆形成能力和多能性等内在特性，以及在体内更长的半衰期，可能使正常成体干细胞更容易积累导致肿瘤转化的基因突变，正如癌症干细胞假说所预测的那样。肿瘤形成也与胚胎干细胞的多能性有关，并且可能是成熟细胞完全去分化的结果，如最近对诱导多能干细胞所报道的那样。肿瘤起始细胞表型可能源于影响调控典型干细胞过程（如自我更新和多能性）的关键基因表达的遗传改变，此外还涉及决定干细胞衰老或寿命的基因。对癌症干细胞及其相应正常对应物进行详细的全基因组分析将有助于阐明肿瘤的细胞和分子本质，提供有关恶性转化起始步骤的基础信息。设计检测此类遗传和表观遗传改变以及显示这些改变的细胞群体的方法，将有助于在癌症发展的早期阶段进行医学干预，从而提高获得良好临床结果的机会。
