Walter Romina Judith, Sonnentag Steffen Joachim, Orian-Rousseau Véronique, Munoz-Sagredo Leonel
Karlsruhe Institute of Technology, Institute of Biological and Chemical Systems-Functional Molecular Systems, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, Germany.
Faculty of Medicine, University of Valparaiso, Angamos 655, Vina del Mar 2540064, Chile.
Cancers (Basel). 2021 Feb 22;13(4):918. doi: 10.3390/cancers13040918.
The cancer stem cell hypothesis poses that the bulk of differentiated cells are non-tumorigenic and only a subset of cells with self-renewal capabilities drive tumor initiation and progression. This means that differentiation could have a tumor-suppressive effect. Accumulating evidence shows, however, that in some solid tumors, like colorectal cancer, such a hierarchical organization is necessary. The identification of Lgr5 as a reliable marker of normal intestinal epithelial stem cells, together with strategies to trace cell lineages within tumors and the possibility to selectively ablate these cells, have proven the relevance of Lgr5 cells for cancer progression. On the contrary, the role of Lgr5 cells during this process remains largely unknown. In this review, we explore available evidence pointing towards possible selective advantages of cancer cells organized hierarchically and its resulting cell heterogeneity. Clear evidence of plasticity between cell states, in which loss of Lgr5 cells can be replenished by dedifferentiation of Lgr5 cells, shows that cell hierarchies could grant adaptive traits to tumors upon changing selective pressures, including those derived from anticancer therapy, as well as during tumor progression to metastasis.
癌症干细胞假说认为，大部分分化细胞无致瘤性，只有一小部分具有自我更新能力的细胞驱动肿瘤的起始和进展。这意味着分化可能具有肿瘤抑制作用。然而，越来越多的证据表明，在一些实体瘤中，如结直肠癌，这种层次结构是必要的。Lgr5被鉴定为正常肠上皮干细胞的可靠标志物，连同追踪肿瘤内细胞谱系的策略以及选择性消融这些细胞的可能性，已经证明了Lgr5细胞与癌症进展的相关性。相反，Lgr5细胞在此过程中的作用在很大程度上仍然未知。在这篇综述中，我们探讨了现有证据，这些证据指向了分层组织的癌细胞可能具有的选择性优势及其导致的细胞异质性。细胞状态之间可塑性的明确证据，即Lgr5细胞的缺失可以通过Lgr5细胞的去分化来补充，表明细胞层次结构可以赋予肿瘤在变化的选择压力下的适应性特征，包括那些来自抗癌治疗的压力，以及在肿瘤进展到转移的过程中。
