侵袭性乳腺癌细胞系 MDA-MB-231 中的干细胞样细胞表达一组独特的 Eph 受体和 Ephrin 配体。
Stem-like Cells from Invasive Breast Carcinoma Cell Line MDA-MB-231 Express a Distinct Set of Eph Receptors and Ephrin Ligands.
机构信息
Department of Basic Medical Sciences, Western University of Health Sciences, Pomona, CA, U.S.A.
出版信息
Cancer Genomics Proteomics. 2020 Nov-Dec;17(6):729-738. doi: 10.21873/cgp.20227.
BACKGROUND/AIM: Breast cancer cell lines consist of bulk tumor cells and a small proportion of stem-like cells. While the bulk cells are known to express a distinct combination of Eph receptors and ephrin ligands, the transcript profiles of stem-like cells in these cell lines have not been adequately characterized. The aim of this study was to determine Eph receptor/ephrin ligand profiles of cancer stem cells specific to a triple negative breast carcinoma cell line.
MATERIALS AND METHODS
The normal breast cell line MCF10A and the invasive breast carcinoma cell line MDA-MB-231 were used to isolate CD24/CD24 cell populations. The profiles of Eph receptors and ephrin ligands were determined by real-time PCR and the relative abundance in bulk and stem cells were compared.
RESULTS
Based on the mean ΔCT values, the descending order of abundance was as follows. Ephrin-A5 > EPHA2 > (EPHA8, EPHB2) > ephrin-B2 > (EPHA7, EPHB4, ephrin-A4) > ephrin-A3 > ephrin-A1 > (EPHB3, ephrin-B1) > EPHA4 > EPHA1 > EPHA10. EPHA6 and ephrin-A2 transcripts were not detectable in stem cells from either cell line. The expression of EPHA4, EPHA7, EPHA8, and ephrin-A5 in MDA-MB-231 stem cells was up-regulated by 12, 20, ~500, and 6.5-fold respectively.
CONCLUSION
The up-regulation of transcripts for EPHA8 and its cognate ligand, ephrin-A5, in the stem cells isolated from MDA-MB-231, suggest their involvement in the invasiveness of this cell line. Based on literature reports, we propose the role of EPHA8 and ephrin-A5 in MDA-MB-231 stem cells via the PI3K-AKT-mTOR pathway.
背景/目的：乳腺癌细胞系由大量肿瘤细胞和一小部分干细胞样细胞组成。尽管已知大量细胞表达独特的 Eph 受体和 Ephrin 配体组合，但这些细胞系中干细胞样细胞的转录谱尚未得到充分表征。本研究旨在确定特定于三阴性乳腺癌细胞系的癌症干细胞的 Eph 受体/Ephrin 配体谱。
材料和方法
使用正常乳腺细胞系 MCF10A 和侵袭性乳腺癌细胞系 MDA-MB-231 分离 CD24/CD24 细胞群。通过实时 PCR 确定 Eph 受体和 Ephrin 配体的图谱，并比较大量细胞和干细胞中的相对丰度。
结果
基于平均 ΔCT 值，丰度的降序如下。Ephrin-A5>EPHA2>（EPHA8、EPHB2）>ephrin-B2>（EPHA7、EPHB4、ephrin-A4）>ephrin-A3>ephrin-A1>（EPHB3、ephrin-B1）>EPHA4>EPHA1>EPHA10。来自两种细胞系的干细胞中均未检测到 EPHA6 和 ephrin-A2 转录本。EPHA4、EPHA7、EPHA8 和 ephrin-A5 在 MDA-MB-231 干细胞中的表达分别上调了 12、20、~500 和 6.5 倍。
结论
从 MDA-MB-231 中分离的干细胞中 Ephrin-A5 的上调及其同源配体 EPHA8 的上调表明它们参与了该细胞系的侵袭性。根据文献报道，我们提出了 EPHA8 和 ephrin-A5 在 MDA-MB-231 干细胞中通过 PI3K-AKT-mTOR 途径发挥作用。
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