图1:原发性和转移性乳腺癌细胞的单细胞RNA测序图谱。a图示来自L2T或l2g标记的TNBC PDX(小鼠1和2)或MDA-MB-231肿瘤(小鼠3)携带的小鼠，包括原发性乳腺肿瘤和肺转移瘤(早期微转移瘤)的排序细胞的单细胞RNA测序。b热图表示在原发肿瘤细胞和肺转移瘤中ICAM1和共表达的茎性特征基因的对数尺度(红色)表达量估计(N = 3只小鼠，2只具有TN PDXs, 1只具有MDA-MB-231肿瘤)。基因是根据它们在所有细胞中与ICAM1的相关性进行排序的，如右边的灰色条所示(从上到下)。底表CD44、GAPDH、ACTB、eGFP、tdTomato作为对照基因，在原发肿瘤细胞与肺转移之间无明显变化。c用流式细胞术检测不同乳腺癌PDX模型(TN1、TN2、TN3)中L2T+或L2G+原发肿瘤细胞和肺转移灶中ICAM1的代表性表达。流型门如图补充图1d所示。d来自c.的PDX原发肿瘤和肺转移瘤中ICAM1差异表达的定量数据。每个模型的生物重复(小鼠)为3个。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
