Methylation state of latent and proliferative metastatic tumor cells

During metastasis, cancer cells travel the circulation to colonise distant sites. Due to the rarity of these events, the immediate cell fate decisions of metastasising tumour cells (mTC) are poorly understood and the role of the endothelium, as dissemination interface, remains elusive. Using a novel combinatorial mTC enrichment approach, we provide a first transcriptional blueprint of the early colonisation process Mice were injected intravenously with 4T1 breast cancer tumor cells. 3.5 days post-injection, latent and proliferative tumor cells were extracted from the lungs and subjected to WGBS. Comparative analysis of DNA methylation of latent vs. proliferative metastatic tumor cells.

在肿瘤转移过程中，癌细胞会通过循环系统迁移并定植于远端器官。由于此类转移事件较为罕见，我们对转移性肿瘤细胞（metastasising tumour cells, mTC）的即时细胞命运决定机制知之甚少，而内皮细胞作为肿瘤播散界面所发挥的作用也尚未明确。本研究通过一种新型联合式mTC富集方法，首次揭示了早期定植过程的转录组蓝图。实验中，我们向小鼠静脉注射4T1乳腺癌细胞。注射后3.5天，我们从小鼠肺部分离出潜伏态与增殖态肿瘤细胞，并对其进行全基因组亚硫酸氢盐测序（Whole Genome Bisulfite Sequencing, WGBS）。最终对潜伏态与增殖态转移性肿瘤细胞的DNA甲基化水平开展了比较分析。