Shao Jun, Fan Wei, Ma Biao, Wu Yiping
Department of Plastic Surgery, Wuhan Tongji Hospital, Wuhan, Hubei 430030, P.R. China.
Department of Breast Cancer, Hubei Cancer Hospital, Wuhan, Hubei 430079, P.R. China.
Mol Med Rep. 2016 Dec;14(6):4991-4998. doi: 10.3892/mmr.2016.5899. Epub 2016 Oct 27.
Identification and isolation of breast cancer stem cells (CSCs) based on CD44/CD24 expression and/or enzymatic activity of aldehyde dehydrogenase 1 (ALDH1). However, the differences among the CD44+/CD24‑/low cells, ALDH1+ cells and the overlap between the sub‑populations have not been frequently investigated. Thus, it is imperative to improve the understanding of breast CSC with different stem markers. CD44+/CD24‑/low, ALDH1+ and ALDH1+CD44+/CD24‑/low cell populations were isolated from fresh breast cancer tissues and analyzed by flow cytometry and immunofluorescence. Mammosphere formation, cell proliferation assay and Transwell experiments, were used to analyze self‑renewal, proliferation and invasion, respectively, for each sub‑population. Finally, in vivo experimentation in mice was performed to evaluate the tumorigenic abilities of the sub‑populations. The sub‑populations of CD44+/CD24‑/low, ALDH1+ and ALDH1+CD44+/CD24‑/low in human breast cancer cells, represented the 7.2, 4.6 and 1.5% of the total tumor cell population, respectively. ALDH1+CD44+/CD24‑/low cells had the strongest ability of self‑renewal, invasion, proliferation and tumorigenicity compared with the other sub‑populations (P<0.05). In conclusion, different phenotypes of CD44+/CD24‑/low, ALDH1+ and ALDH1+CD44+/CD24‑/low were isolated and demonstrated that breast CSCs are heterogeneous, and they exhibit distinct biological characteristics. As ALDH1+CD44+/CD24‑/low cells demonstrated the strongest stem‑like properties, it may be a useful specific stem cell marker. The utilization of more reliable biomarkers to distinguish the breast CSC pool will be important for the development of specific target therapies for breast cancer.
基于CD44/CD24表达和/或醛脱氢酶1（ALDH1）的酶活性来鉴定和分离乳腺癌干细胞（CSCs）。然而，CD44+/CD24‑/低细胞、ALDH1+细胞之间的差异以及亚群之间的重叠情况尚未得到充分研究。因此，有必要加深对具有不同干细胞标志物的乳腺CSC的理解。从新鲜乳腺癌组织中分离出CD44+/CD24‑/低、ALDH1+和ALDH1+CD44+/CD24‑/低细胞群体，并通过流式细胞术和免疫荧光进行分析。分别使用乳腺球形成、细胞增殖测定和Transwell实验来分析每个亚群的自我更新、增殖和侵袭能力。最后，在小鼠体内进行实验以评估亚群的致瘤能力。人乳腺癌细胞中的CD44+/CD24‑/低、ALDH1+和ALDH1+CD44+/CD24‑/低亚群分别占肿瘤细胞总数的7.2%、4.6%和1.5%。与其他亚群相比，ALDH1+CD44+/CD24‑/低细胞具有最强的自我更新、侵袭、增殖和致瘤能力（P<0.05）。总之，分离出了CD44+/CD24‑/低、ALDH1+和ALDH1+CD44+/CD24‑/低的不同表型，证明乳腺CSCs具有异质性，并且它们表现出不同的生物学特征。由于ALDH1+CD44+/CD24‑/低细胞表现出最强的干细胞样特性，它可能是一种有用的特异性干细胞标志物。利用更可靠的生物标志物来区分乳腺CSC库对于开发乳腺癌的特异性靶向治疗将具有重要意义。
