Vilardo Laura, Pelucchi Paride, Brindisi Antonia, Abeni Edoardo, Piscitelli Eleonora, Mosca Ettore, Bertalot Giovanni, Palizban Mira, Karnavas Theodoros, Gritzapis Angelos D, Misitzis Ioannis, Götte Martin, Zucchi Ileana, Reinbold Rolland
Institute of Biomedical Technologies, National Research Council, 20054 Milano, Italy.
Unita' Operativa Multizonale di Anatomia Patologica, APSS and Centre for Medical Sciences-CISMed, University of Trento, 38122 Trento, Italy.
Cells. 2025 Aug 13;14(16):1246. doi: 10.3390/cells14161246.
Clonally established tumor cell lines often do not recapitulate the behavior of cells in tumors. The sequencing of a whole tumor tissue may not uncover transcriptome profiles induced by the interactions of all different cell types within a tumor. Interferons for instance have a vast number of binding sites in their target genes. Access to the DNA binding sites is determined by the epigenomic state of each different cell type within a tumor mass. To understand how genes such as interferons appear to have both tumor-promoting and tumor-inhibiting functions, single-cell transcript analysis was performed in the breast cancer tissue of + (epidermal growth factor receptor 2) patients. We identified that potential antagonistic oncogenic activities of cells can be due to diverse expression patterns of genes with pleiotropic functions. Molecular pathways both known and novel were identified and were similar with those previously identified for patients with rheumatoid arthritis. Our study demonstrates the efficacy in using single-cell transcript analysis to gain insight into genes with apparent contradictory or paradoxical roles in oncogenesis.
克隆建立的肿瘤细胞系通常不能重现肿瘤中细胞的行为。对整个肿瘤组织进行测序可能无法揭示肿瘤内所有不同细胞类型相互作用所诱导的转录组图谱。例如，干扰素在其靶基因中有大量结合位点。DNA结合位点的可及性由肿瘤块内每种不同细胞类型的表观基因组状态决定。为了了解诸如干扰素等基因如何似乎同时具有促肿瘤和抑肿瘤功能，我们对表皮生长因子受体2阳性患者的乳腺癌组织进行了单细胞转录分析。我们发现细胞潜在的拮抗致癌活性可能归因于具有多效性功能的基因的不同表达模式。我们鉴定出了已知和新的分子途径，这些途径与先前在类风湿性关节炎患者中鉴定出的途径相似。我们的研究证明了使用单细胞转录分析来深入了解在肿瘤发生中具有明显矛盾或相悖作用的基因的有效性。
