Division of Stem Cell Biology, Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo, 060-0815, Japan.
Semin Cancer Biol. 2022 Jul;82:176-183. doi: 10.1016/j.semcancer.2020.12.003. Epub 2021 Jan 13.
Glioblastoma (GBM) and other malignant tumours consist of heterogeneous cancer cells, including GBM-initiating cells (GICs). This heterogeneity is likely to arise from the following: different sets of genetic mutations and epigenetic modifications, which GICs gain in the transformation process; differences in cells of origin, such as stem cells, precursor cells or differentiated cells; and the cancer microenvironment, in which GICs communicate with neural cells, endothelial cells and immune cells. Furthermore, considering that various types of GICs can be generated at different time points of the transformation process, GBM very likely consists of heterogeneous GICs and their progeny. Because cancer cell heterogeneity is responsible for therapy resistance, it is crucial to develop methods of reducing such heterogeneity. Here, I summarize how GIC heterogeneity is generated in the transformation process and present how cell heterogeneity in cancer can be addressed based on recent findings.
胶质母细胞瘤 (GBM) 和其他恶性肿瘤由异质性癌细胞组成，包括胶质母细胞瘤起始细胞 (GICs)。这种异质性可能源于以下几个方面：不同的基因突变和表观遗传修饰组，GIC 在转化过程中获得这些改变；不同的起源细胞，如干细胞、前体细胞或分化细胞；以及肿瘤微环境，GIC 与神经细胞、内皮细胞和免疫细胞相互作用。此外，考虑到不同类型的 GIC 可以在转化过程的不同时间点产生，GBM 很可能由异质的 GIC 及其后代组成。由于癌细胞异质性是导致治疗耐药的原因，因此开发减少这种异质性的方法至关重要。在这里，我总结了 GIC 异质性在转化过程中是如何产生的，并根据最近的发现介绍了如何解决癌症中的细胞异质性问题。
