Chair of Immunology, Center for Biomedical Education and Research (ZBAF), Witten/Herdecke University, Stockumer Str. 10, 58448 Witten, Germany.
Cells. 2019 Feb 7;8(2):132. doi: 10.3390/cells8020132.
Current strategies to determine tumor × normal (TN)-hybrid cells among human cancer cells include the detection of hematopoietic markers and other mesodermal markers on tumor cells or the presence of donor DNA in cancer samples from patients who had previously received an allogenic bone marrow transplant. By doing so, several studies have demonstrated that TN-hybrid cells could be found in human cancers. However, a prerequisite of this cell fusion search strategy is that such markers are stably expressed by TN-hybrid cells over time. However, cell fusion is a potent inducer of genomic instability, and TN-hybrid cells may lose these cell fusion markers, thereby becoming indistinguishable from nonfused tumor cells. In addition, hybrid cells can evolve from homotypic fusion events between tumor cells or from heterotypic fusion events between tumor cells and normal cells possessing similar markers, which would also be indistinguishable from nonfused tumor cells. Such indistinguishable or invisible hybrid cells will be referred to as dark matter hybrids, which cannot as yet be detected and quantified, but which contribute to tumor growth and progression.
目前，在人类癌细胞中确定肿瘤-正常（TN）杂交细胞的策略包括检测肿瘤细胞上的造血标记物和其他中胚层标记物，或者在先前接受同种异体骨髓移植的患者的癌症样本中存在供体 DNA。通过这样做，几项研究已经表明，TN-杂交细胞可以在人类癌症中找到。然而，这种细胞融合搜索策略的一个前提条件是，随着时间的推移，这些标记物能够稳定地表达于 TN-杂交细胞。然而，细胞融合是基因组不稳定性的一个有力诱导因素，TN-杂交细胞可能会失去这些细胞融合标记物，从而变得与未融合的肿瘤细胞无法区分。此外，杂交细胞可以通过肿瘤细胞之间的同型融合事件或通过肿瘤细胞与具有相似标记物的正常细胞之间的异型融合事件进化而来，这也与未融合的肿瘤细胞无法区分。这些无法区分或不可见的杂交细胞将被称为暗物质杂交细胞，它们目前无法被检测和定量，但它们有助于肿瘤的生长和进展。
