Laboratory for Cancer Biology, Cancer Institute (WIA), Chennai, Tamilnadu, India.
Department of Molecular Oncology, Cancer Institute (WIA), Chennai, India.
Exp Cell Res. 2020 Jul 1;392(1):112009. doi: 10.1016/j.yexcr.2020.112009. Epub 2020 Apr 17.
One of the reasons for recurrence following treatment of high grade serous ovarian carcinoma (HGSOC) is the persistence of residual cancer stem cells (CSCs). There has been variability between laboratories in the identification of CSC markers for HGSOC. We have identified new surface markers (CD24, CD9 and EPHA1) in addition to those previously known (CD44, CD117 and CD133) using a bioinformatics approach. The expression of these surface markers was evaluated in ovarian cancer cell lines, primary malignant cells (PMCs), normal ovary and HGSOC. There was no preferential expression of any of the markers or a combination. All the markers were expressed at variable levels in ovarian cancer cell lines and PMCs. Only CD117 and CD9 were expressed in the normal ovarian surface epithelium and fallopian tube. Both ALDEFLUOR (ALDH1A1) and side population assays identified a small proportion of cells (<3%) separately that did not overlap with little variability in cell lines and PMCs. All surface markers were co-expressed in ALDH1A1+ cells without preference for one combination. The cell cycle analysis of ALDH1A1+ cells alone revealed that majority of them reside in G0/G1 phase of cell cycle. Further separation of G0 and G1 phases showed that ALDH1A1+ cells reside in G1 phase of the cell cycle. Xenograft assays showed that the combinations of ALDH1A1 + cells co-expressing CD9, CD24 or EPHA1 were more tumorigenic and aggressive with respect to ALDH1A1-cells. These data suggest that a combined approach could be more useful in identifying CSCs in HGSOC.
高级别浆液性卵巢癌（HGSOC）治疗后复发的原因之一是残留的癌症干细胞（CSC）的存在。在识别 HGSOC 的 CSC 标志物方面，不同实验室之间存在差异。我们使用生物信息学方法除了先前已知的标志物（CD44、CD117 和 CD133）外，还鉴定了新的表面标志物（CD24、CD9 和 EPHA1）。在卵巢癌细胞系、原发性恶性细胞（PMCs）、正常卵巢和 HGSOC 中评估了这些表面标志物的表达。这些标志物没有任何一种或组合的优先表达。所有标志物在卵巢癌细胞系和 PMCs 中的表达水平不同。只有 CD117 和 CD9 在正常卵巢表面上皮和输卵管中表达。ALDEFLUOR（ALDH1A1）和侧群测定分别单独鉴定出一小部分（<3%）细胞，与细胞系和 PMCs 中的细胞无重叠，且变化很小。所有表面标志物在 ALDH1A1+细胞中共同表达，没有一种组合具有偏好性。ALDH1A1+细胞的细胞周期分析单独显示，它们中的大多数处于细胞周期的 G0/G1 期。进一步分离 G0 和 G1 期表明 ALDH1A1+细胞位于细胞周期的 G1 期。异种移植试验表明，共表达 CD9、CD24 或 EPHA1 的 ALDH1A1+细胞组合与 ALDH1A1-细胞相比，具有更强的致瘤性和侵袭性。这些数据表明，联合方法可能更有助于识别 HGSOC 中的 CSC。
