图1:比较原发性和转移性肿瘤部位乳腺癌细胞的单细胞RNA测序谱。a显示从L2T或l2g标记的TNBC PDX(小鼠1和2)或MDA-MB-231肿瘤(小鼠3)小鼠(原发性乳腺肿瘤和肺转移(早期微转移)中分选细胞的单细胞RNA测序的示意图。b热图表示原发肿瘤细胞和肺转移(N = 3只小鼠，2只为TN PDXs, 1只为MDA-MB-231肿瘤)中ICAM1和共表达的干性特征基因的对数级表达量估计(红色)。基因是根据它们在所有细胞中与ICAM1的相关性进行排序的，如右侧的灰色条所示(从上至下)。底表CD44、GAPDH、ACTB、eGFP、tdTomato作为对照基因，在原发肿瘤细胞和肺转移间无明显变化。c通过流式细胞术检测不同乳腺癌PDX模型(TN1、TN2和TN3)中L2T+或L2G+原发肿瘤细胞和肺转移灶中ICAM1的代表性表达。流量剖面闸门如图补充图1d所示。d来自c. PDX原发肿瘤与肺转移中ICAM1差异表达的定量数据。每个模型n = 3个生物重复(小鼠)。单侧t检验*P = 0.04;** p = 0.01; *P = 0.02. The boxes range from the first to third quartile with x in a box indicating mean value and whisker lines extending to outliers (minimum and maximum). e Representative IHC staining images of ICAM1 expression (brown color) in primary tumors and lung metastases from PDX TN1 and TN2 models validating c and d. f Distribution of ICAM1 expression across PAM50 subtypes in the TCGA BRCA cohort (N = 1037). Basal-like and HER2-enriched subtypes are the top two exhibiting significantly higher ICAM1 expression as compared to normal breast tissue (percentage of cases above the blue line value are shown for each subtype). Statistical significance was assessed using a two-sided Student’s t test. *P < 0.05, **P < 0.01, and ****P ≤ 0.0001. g Schematic and flow histogram analyses of the orthotopically implanted TN1-PDX tumors with or without ICAM1 overexpression (OE) at the 4th mammary fat pads. h. PDX TN1 tumor weights 2 months after orthotopic injections of TN1 cells with ICAM1 OE and control vector (Con) (2.5e5 cells into one mammary fat pad/mouse). n = 3 mice per cell group. Two-sided t test *P = 0.04. The boxes range from the first to third quartile with x in a box indicating mean value and whisker lines extending to outliers (minimum and maximum). i, j Representative lung images and normalized BLI signals (total flux) of spontaneous lung metastases in orthotopically implanted ICAM1 OE and control TN1 tumor-bearing mice as in g, h. n = 3 mice per group. Two-sided t test **P = 0.003. The boxes range from the first to third quartile with x in a box indicating mean value and whisker lines extending to outliers (minimum and maximum). k Schematic and flow histogram analyses of tail vein injected MDA-MB-231 tumor cells transfectd with siRNA control (siCon) and siICAM1. l, m. Representative images and quantitative data of BLI signal of mice injected with siCon and siICAM1-transfected MDA-MB-231 cells via tail vein (n = 4 mice per cell group. Two-sided t test **P = 0.01 for time point comparisons. N = 6 independent experiments). The boxes range from the first to third quartile with x in a box indicating mean value and whisker lines extending to outliers (minimum and maximum). Credit: DOI: 10.1038/s41467-021-25189-z
