School of Biomedical Sciences, Institute of Clinical Sciences, University of Birmingham, Birmingham B15 2TT, UK.
School of Law, University of Salamanca, 37007 Salamanca, Spain.
Int J Mol Sci. 2019 Dec 19;21(1):45. doi: 10.3390/ijms21010045.
Cancer-stem-cell theory states that most, if not all, cancers arise from a stem/uncommitted cell. This theory revolutionised our view to reflect that cancer consists of a hierarchy of cells that mimic normal cell development. Elegant studies of twins who both developed acute lymphoblastic leukaemia in childhood revealed that at least two genomic insults are required for cancer to develop. These 'hits' do not appear to confer a growth advantage to cancer cells, nor do cancer cells appear to be better equipped to survive than normal cells. Cancer cells created by investigators by introducing specific genomic insults generally belong to one cell lineage. For example, transgenic mice in which the LIM-only 2 (,associated with human acute T-lymphoblastic leukaemia) and (associated with human chronic myeloid leukaemia) oncogenes were active solely within the haematopoietic stem-cell compartment developed T-lymphocyte and neutrophil lineage-restricted leukaemia, respectively. This recapitulated the human form of these diseases. This 'hardwiring' of lineage affiliation, either throughout leukaemic stem cell development or at a particular stage, is different to the behaviour of normal haematopoietic stem cells. While normal cells directly commit to a developmental pathway, they also remain versatile and can develop into a terminally differentiated cell that is not part of the initial lineage. Many cancer stem cells do not have this versatility, and this is an essential difference between normal and cancer stem cells. In this report, we review findings that support this notion.
癌症干细胞理论指出，大多数（如果不是全部）癌症都源于干细胞/未分化细胞。这一理论彻底改变了我们的观点，反映出癌症由类似于正常细胞发育的细胞层级组成。对同时在儿童时期罹患急性淋巴细胞白血病的双胞胎进行的优雅研究表明，癌症的发展至少需要两次基因组损伤。这些“打击”似乎不会赋予癌细胞生长优势，癌细胞也似乎没有比正常细胞更有能力生存。研究人员通过引入特定的基因组损伤来创建的癌细胞通常属于一种细胞谱系。例如，转基因小鼠中，LIM 仅 2（与人类急性 T 淋巴细胞白血病相关）和 （与人类慢性髓性白血病相关）癌基因仅在造血干细胞区室中活跃，分别发展为 T 淋巴细胞和中性粒细胞谱系受限的白血病。这再现了人类形式的这些疾病。这种谱系归属的“硬连线”，无论是在白血病干细胞发育的整个过程中还是在特定阶段，都与正常造血干细胞的行为不同。虽然正常细胞直接承诺进行发育途径，但它们仍然具有多功能性，可以发育成不属于初始谱系的终末分化细胞。许多癌症干细胞没有这种多功能性，这是正常和癌症干细胞之间的一个重要区别。在本报告中，我们回顾了支持这一观点的发现。
