Institute of Immunology, Centre for Biomedical Education and Research (ZBAF), Witten/Herdecke University, Stockumer Str. 10, 58448, Witten, Germany.
Biochemistry and Tumor Biology Laboratory, Department of Obstetrics and Gynaecology, Hannover Medical School, 30625, Hannover, Germany.
Cell Commun Signal. 2023 Apr 4;21(1):68. doi: 10.1186/s12964-023-01085-5.
Cellular fusion e.g. between cancer cells and normal cells represents a stepwise process that is tightly regulated. During a pre-hybrid preparation program somatic cells and/or cancer cells are promoted to a pro-fusogenic state as a prerequisite to prepare a fusion process. A pro-fusogenic state requires significant changes including restructure of the cytoskeleton, e.g., by the formation of F-actin. Moreover, distinct plasma membrane lipids such as phosphatidylserine play an important role during cell fusion. In addition, the expression of distinct fusogenic factors such as syncytins and corresponding receptors are of fundamental importance to enable cellular mergers. Subsequent hybrid formation and fusion are followed by a post-hybrid selection process. Fusion among normal cells is important and often required during organismal development. Cancer cells fusion appears more rarely and is associated with the generation of new cancer hybrid cell populations. These cancer hybrid cells contribute to an elevated tumour plasticity by altered metastatic behaviour, changes in therapeutic and apoptotic responses, and even in the formation of cancer stem/ initiating cells. While many parts within this multi-step cascade are still poorly understood, this review article predominantly focusses on the intracellular necessities for fusion among cancer cells or with other cell populations of the tumour microenvironment. Video Abstract.
细胞融合，例如癌细胞和正常细胞之间的融合，代表了一个逐步的过程，这个过程受到严格的调控。在杂交前的准备阶段，体细胞和/或癌细胞被促进进入促融合状态，这是准备融合过程的前提。促融合状态需要包括细胞骨架重构在内的重大变化，例如通过 F-肌动蛋白的形成。此外，在细胞融合过程中，不同的质膜脂质，如磷脂酰丝氨酸，起着重要的作用。此外，特定的融合因子，如合胞蛋白及其相应的受体的表达，对于实现细胞融合至关重要。随后的杂交形成和融合伴随着杂交后的选择过程。正常细胞之间的融合在生物体发育过程中很重要，而且经常需要。癌细胞的融合出现得更罕见，与新的癌细胞杂交细胞群的产生有关。这些癌细胞杂交细胞通过改变转移行为、治疗和凋亡反应的变化，甚至在形成癌症干细胞/起始细胞方面，对提高肿瘤的可塑性做出贡献。尽管这个多步骤级联中的许多部分仍然了解甚少，但这篇综述文章主要侧重于癌细胞之间或与肿瘤微环境中其他细胞群体融合的细胞内必要性。视频摘要。
