Tissue Regeneration in the Chronically Inflamed Tumor Environment: Implications for Cell Fusion Driven Tumor Progression and Therapy Resistant Tumor Hybrid Cells.
Tissue Regeneration in the Chronically Inflamed Tumor Environment: Implications for Cell Fusion Driven Tumor Progression and Therapy Resistant Tumor Hybrid Cells.
复制标题
DOI：
10.3390/ijms161226240
复制
发表时间：
2015-12-19
影响因子：
5.6
通讯作者：
Zänker KS
中科院分区：
文献类型：
--
作者：
Dittmar T;Zänker KS
在癌症背景下细胞融合的生物学现象仍然是一个有争议的辩论。尽管在过去的几十年中已经发表了大量的体外和体内数据，但肿瘤杂交细胞可能起源于（人类）癌症并可能导致疾病进展的最终证据仍然缺失，这表明细胞融合假说是虚构的而不是事实。然而，缺乏这一最终证据是反对这一假设的有效论据，特别是如果人们不得不考虑适当的标志物（尚未）存在，从而使其几乎不可能将人类肿瘤细胞明确鉴定为肿瘤杂交细胞。本文就支持细胞融合在肿瘤中的应用进行综述。此外，我们将完善细胞融合假说，提供证据表明，细胞融合是一个强有力的诱导剂的非整倍性，基因组的不稳定性，最有可能的是，甚至chromothripsis，这表明细胞融合，突变和非整倍性，可能是一个诱变剂表型诱导。最后，我们将证明癌症治疗期间“意外”的组织修复过程可能导致耐药癌症杂交干细胞的起源。
The biological phenomenon of cell fusion in a cancer context is still a matter of controversial debates. Even though a plethora of in vitro and in vivo data have been published in the past decades the ultimate proof that tumor hybrid cells could originate in (human) cancers and could contribute to the progression of the disease is still missing, suggesting that the cell fusion hypothesis is rather fiction than fact. However, is the lack of this ultimate proof a valid argument against this hypothesis, particularly if one has to consider that appropriate markers do not (yet) exist, thus making it virtually impossible to identify a human tumor cell clearly as a tumor hybrid cell. In the present review, we will summarize the evidence supporting the cell fusion in cancer concept. Moreover, we will refine the cell fusion hypothesis by providing evidence that cell fusion is a potent inducer of aneuploidy, genomic instability and, most likely, even chromothripsis, suggesting that cell fusion, like mutations and aneuploidy, might be an inducer of a mutator phenotype. Finally, we will show that “accidental” tissue repair processes during cancer therapy could lead to the origin of therapy resistant cancer hybrid stem cells.