转录组分析鉴定肺转移定植期间反应性ec的特征性变化。a，免疫荧光图像显示，在静脉注射MDA231-LM2乳腺癌细胞后的指定时间点，小鼠肺中肺ECs (CD31)与转移性乳腺癌细胞(GFP)的相关性。比例尺，50 μm。虚线表示转移灶边缘。b, a转移结节伴结节内ECs的定量;在每个时间点分析4只小鼠的N = 72个结节(第1周)，N = 76个结节(第2周)和N = 83个结节(第3周)。数据以均数±s.e.m表示。c，第1-3周时mda231 - lm2来源的肺转移结节大小。每个肺至少分析16个结节;每组4只。 d, MDA231-LM2 cancer cells (left) and ECs (right) in lung at indicated time points. Data show means ± s.d; n = 4 mice per time point. P values were determined by one-way ANOVA with Dunnett’s multiple comparison test. e, Experimental setup for EC isolation from mouse lung at different stages of MDA231-LM2-derived metastasis, followed by transcriptomic analysis. f, PC analysis of gene expression profiles from ECs isolated from healthy lung (control) or lung with different stages of metastasis (as in e). g, GSEA of isolated ECs using proliferation- or inflammation-related signatures. Signatures with nominal P < 0.05 and FDR < 0.25 were considered significant. h,i, Violin plots showing z-score analysis of tumor angiogenesis and tip cell signatures (h) or patient poor-outcome gene clusters (i), calculated from transcriptomic profiles of ECs isolated from metastatic lungs at indicated time points. P values were determined using averaged z-scores of each signature by unpaired two-tailed t-test; n = 3 biological replicates per group. j, Heatmap showing expression of 58 genes of secreted proteins (GSP58) upregulated in lung ECs at week 3 post cancer cell injection. Cutoff log2(fold change (FC)) > 0.75, P < 0.05, FDRq < 0.25. k, GSEA graph showing enrichment of GSP58 in samples of human lung metastases of breast cancer, ranked according to lung metastasis-free survival. NES, normalized enrichment score. FDR was determined from P values calculated by random permutation test. Credit:自然癌症(2022)。DOI: 10.1038 / s43018 - 022 - 00353 - 6
Oskarsson现在在佛罗里达州坦帕市的H. Lee Moffitt癌症中心和研究所工作，他总结道:“这种相互对话的复杂性癌症细胞，巨噬细胞和内皮细胞是惊人的。随着对这些转移相互作用中涉及的众多蛋白质和其他因素的更好理解，我们能够确定对抗乳腺癌转移的新策略的各种起点。我们已经为此开发了初步的治疗概念，现在我们需要在进一步的研究中验证。”
