Neural stemness contributes to cell tumorigenicity.
Neural stemness contributes to cell tumorigenicity.
复制标题
神经干性有助于细胞致瘤性
DOI：
10.1186/s13578-021-00531-6
复制
发表时间：
2021-01-19
影响因子：
7.5
通讯作者：
Cao Y
中科院分区：
文献类型：
--
作者：
Xu L;Zhang M;Shi L;Yang X;Chen L;Cao N;Lei A;Cao Y
研究背景以往的研究表明，肿瘤的发生与神经系统有关。近年来，越来越多的研究发现肿瘤细胞与神经干/祖细胞具有相同的特性和调控网络。然而，神经干细胞和细胞tumorigenicity的属性之间的关系是unknow.ResultsWe表明，神经干/祖细胞，但不是非神经胚胎或体干/祖细胞类型，表现出致瘤性和分化成组织类型的所有胚层的潜力，当它们被放置在非原生环境中移植到免疫缺陷的裸鼠。同样地，能够引发肿瘤的癌细胞具有神经干细胞的性质，因为除了先前表征的其神经元分化潜能之外，它们在神经干细胞特异性无血清培养基中形成神经球的能力和分化潜能。此外，没有致瘤性的成肌细胞中的促分化因子的丧失导致成肌细胞身份的丧失，并获得神经干细胞性、致瘤性和再分化潜力的性质。相反，通过分化丧失神经干细胞导致致瘤性丧失。提示神经干细胞的特性与细胞的致瘤性有关，肿瘤表型异质性可能是神经干细胞分化潜能的影响。生物信息学分析表明，神经基因除了在神经发育中的作用外，一般与胚胎发育和癌症相关;而非神经基因则不然。大多数神经特异性基因出现在典型的物种中，代表了进化过程中从单细胞到多细胞的过渡。基因inMonosiga brevicollis，单细胞物种，是一个最近的已知的相对后生动物，偏向于神经cells.ConclusionsWe建议，神经干细胞的属性是细胞致瘤性的来源。这是由于神经偏向的单细胞状态是多细胞性的基态，因此在进化过程中细胞类型多样化或分化，并且肿瘤发生是体细胞中神经基态的恢复过程，其沿着由神经状态的进化优势预先确定的默认路线。
BackgroundPrevious studies demonstrated the dependence of cancer on nerve. Recently, a growing number of studies reveal that cancer cells share the property and regulatory network with neural stem/progenitor cells. However, relationship between the property of neural stemness and cell tumorigenicity is unknown.ResultsWe show that neural stem/progenitor cells, but not non-neural embryonic or somatic stem/progenitor cell types, exhibit tumorigenicity and the potential for differentiation into tissue types of all germ layers when they are placed in non-native environment by transplantation into immunodeficient nude mice. Likewise, cancer cells capable of tumor initiation have the property of neural stemness because of their abilities in neurosphere formation in neural stem cell-specific serum-free medium and in differentiation potential, in addition to their neuronal differentiation potential that was characterized previously. Moreover, loss of a pro-differentiation factor in myoblasts, which have no tumorigenicity, lead to the loss of myoblast identity, and gain of the property of neural stemness, tumorigenicity and potential for re-differentiation. By contrast, loss of neural stemness via differentiation results in the loss of tumorigenicity. These suggest that the property of neural stemness contributes to cell tumorigenicity, and tumor phenotypic heterogeneity might be an effect of differentiation potential of neural stemness. Bioinformatic analysis reveals that neural genes in general are correlated with embryonic development and cancer, in addition to their role in neural development; whereas non-neural genes are not. Most of neural specific genes emerged in typical species representing transition from unicellularity to multicellularity during evolution. Genes inMonosiga brevicollis, a unicellular species that is a closest known relative of metazoans, are biased toward neural cells.ConclusionsWe suggest that the property of neural stemness is the source of cell tumorigenicity. This is due to that neural biased unicellular state is the ground state for multicellularity and hence cell type diversification or differentiation during evolution, and tumorigenesis is a process of restoration of neural ground state in somatic cells along a default route that is pre-determined by an evolutionary advantage of neural state.
登录
查看更多内容
影响因子：
5.5
作者：
Dekkers, Ilona A.;Cleven, Arjen;Kroon, Herman M.
通讯作者：
Kroon, Herman M.
影响因子：
50.3
作者：
Drummond CJ;Hanna JA;Garcia MR;Devine DJ;Heyrana AJ;Finkelstein D;Rehg JE;Hatley ME
通讯作者：
Hatley ME
影响因子：
16.6
作者：
Chen, Han;Lin, Fangqin;He, Xionglei
通讯作者：
He, Xionglei
影响因子：
2.4
作者：
Lee, Shih-Han;Jeyapalan, Jennie N.;Scotting, Paul J.
通讯作者：
Scotting, Paul J.
影响因子：
56.9
作者：
Clarke, DL;Johansson, CB;Frisén, J
通讯作者：
Frisén, J