Metastatic cancer is a leading cause of death in cancer patients worldwide. While circulating hybrid cells (CHCs) are implicated in metastatic spread, studies documenting their tissue origin remain sparse, with limited candidate approaches using one–two markers. Utilizing high-throughput single-cell and spatial transcriptomics, we identified tumor hybrid cells (THCs) co-expressing epithelial and macrophage markers and expressing a distinct transcriptome. Rarely, normal tissue showed these cells (NHCs), but their transcriptome was easily distinguishable from THCs. THCs with unique transcriptomes were observed in breast and colon cancers, suggesting this to be a generalizable phenomenon across cancer types. This study establishes a framework for HC identification in large datasets, providing compelling evidence for their tissue residence and offering comprehensive transcriptomic characterization. Furthermore, it sheds light on their differential function and identifies pathways that could explain their newly acquired invasive capabilities. THCs should be considered as potential therapeutic targets.
转移性癌症是全球癌症患者死亡的主要原因。尽管循环杂交细胞（CHCs）被认为与癌症转移扩散有关，但记录其组织来源的研究仍然稀少，且现有研究多局限于使用一至两种标志物的候选方法。通过应用高通量单细胞转录组学与空间转录组学技术，我们鉴定出同时表达上皮细胞和巨噬细胞标志物、并呈现独特转录组特征的肿瘤杂交细胞（THCs）。正常组织中极少出现此类细胞（NHCs），且其转录组特征与THCs存在明显差异。在乳腺癌和结肠癌中均观察到具有独特转录组的THCs，表明这种现象可能普遍存在于多种癌症类型中。本研究建立了在大规模数据集中鉴定杂交细胞的框架，为其组织定位提供了有力证据，并完成了全面的转录组特征解析。此外，研究揭示了这些细胞的功能差异，并识别出可能解释其新获得侵袭能力的信号通路。THCs应被视为潜在的治疗靶点。
肿瘤(癌症)患者之家