Biodynamics Optical Imaging Center (BIOPIC), School of Life Sciences, Peking University, No.5 Yiheyuan Road Haidian District, Beijing, 100871, China.
The CAS Key Laboratory of Innate Immunity and Chronic Disease, Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Science and Medical Center, University of Science & Technology of China, Hefei, Anhui, 230027, China.
Mol Cancer. 2018 Feb 23;17(1):65. doi: 10.1186/s12943-018-0809-x.
Breast cancer stem cells (BCSCs) are thought to be responsible for tumor initiation, metastasis and relapse. Our group and others have described markers useful in isolating BCSCs just as aldehyde dehydrogenase positive (ALDH) or CD24CD44. In fact, cells which simultaneously express both sets of markers have the highest tumor initiating capacity. Although the transcriptomic profile of cells expressing each BCSC marker alone has been reported, the profile of the most tumorigenic population expressing both sets of markers has not. Here we used the biomarker combination of ALDH and CD24/CD44 to sort four populations isolated from triple-negative breast cancer (TNBC) patient-derived xenografts, and performed whole-transcriptome sequencing on each population. We systematically compared the profiles of the three states of BCSCs (ALDHCD24CD44, ALDHnon-CD24CD44 and ALDHCD24CD44) to that of the differentiated tumor cells (ALDHnon-CD24CD44). For the first time, we compared the ALDHCD24CD44 BCSCs with the other two BCSC populations. In ALDHCD24CD44 BCSCs, we identified P4HA2, PTGR1 and RAB40B as potential prognostic markers, which were virtually related to the status of BCSCs and tumor growth in TNBC cells.
乳腺癌干细胞(BCSCs)被认为是肿瘤起始、转移和复发的原因。我们的团队和其他团队已经描述了一些有用的标记物,用于分离 BCSC,如醛脱氢酶阳性(ALDH)或 CD24CD44。事实上,同时表达这两组标记物的细胞具有最高的肿瘤起始能力。尽管已经报道了单独表达每个 BCSC 标记物的细胞的转录组谱,但同时表达这两组标记物的最致瘤性群体的谱尚未报道。在这里,我们使用 ALDH 和 CD24/CD44 生物标志物组合对从三阴性乳腺癌(TNBC)患者来源的异种移植物中分离的四个群体进行排序,并对每个群体进行了全转录组测序。我们系统地比较了三种 BCSC 状态(ALDHCD24CD44、ALDHnon-CD24CD44 和 ALDHCD24CD44)与分化肿瘤细胞(ALDHnon-CD24CD44)的图谱。我们首次将 ALDHCD24CD44 BCSC 与其他两种 BCSC 群体进行了比较。在 ALDHCD24CD44 BCSC 中,我们鉴定出 P4HA2、PTGR1 和 RAB40B 作为潜在的预后标志物,它们与 BCSC 的状态以及 TNBC 细胞中的肿瘤生长密切相关。