Possible involvement of stem-like populations with elevated ALDH1 in sarcomas for chemotherapeutic drug resistance
Possible involvement of stem-like populations with elevated ALDH1 in sarcomas for chemotherapeutic drug resistance
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DOI：
10.3892/or_00000885
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发表时间：
2010-08-01
期刊：
影响因子：
4.2
通讯作者：
Tsujiuchi, Toshifumi
中科院分区：
文献类型：
--
作者：
Honoki, Kanya;Fujii, Hiromasa;Tsujiuchi, Toshifumi
已提出升高的醛脱氢酶1（ALDH 1）作为干细胞标记物的可能候选物之一，所述干细胞标记物可用于从癌症（如白血病和乳腺癌）中分离癌症干细胞。在目前的研究中，我们发现ALDH 1升高的亚群存在于人肉瘤细胞系MG 63（骨肉瘤）和HT 1080（纤维肉瘤）中，使用Aldefluor测定。通过使用FACSAria进行细胞分选，从MG 63细胞系中分离ALDH 1阳性和阴性细胞群。在正常单层培养条件下，两个亚群具有与亲本MG 63类似的分化能力。具有在锚定非依赖性、血清饥饿条件下形成球体的能力的亚群显示除了干细胞相关基因（如Nanog、Oct 3/4、Stat 3和Sox 2）的强mRNA表达之外，ALDH 1 mRNA表达增加，并且具有通过次级球体形成进行自我更新的能力。与单层贴壁细胞相比，MG 63细胞系的肌球细胞对阿霉素和顺铂均表现出较强的化疗耐药性。总之，具有升高的ALDH 1的球形成细胞是肉瘤干细胞的可能候选者，具有强的化学抗性能力。虽然ALDH 1升高不足以代表肉瘤干细胞，但有效的解毒可能有助于人类肉瘤干细胞样球细胞的耐药性。
Elevated aldehyde dehydrogenase 1 (ALDH1) has been proposed as one of the possible candidates for a stem cell maker that can be used for the isolation of cancer stem cells from cancers such as leukemia and breast cancer. In the current study, we found that subpopulations with elevated ALDH1 were present in the human sarcoma cell lines, MG63 (osteosarcoma) and HT 1080 (fibrosarcoma), using Aldefluor assay. Both ALDH1 positive and negative cell populations were isolated from the MG63 cell line, by cell-sorting using FACSAria. Both subpopulations had a comparable ability to differentiate similarly to the parental MG63, under normal monolayer culture condition. Subpopulations with the ability to form spheres in anchorage-independent, serum-starved conditions showed increased ALDH1 mRNA expression in addition to strong mRNA expression of the stem cell-related genes, such as Nanog, Oct3/4, Stat3 and Sox2, and possessed ability for self-renewal with secondary sphere formation. Sarcosphere cells from the MG63 cell line showed strong chemo-resistance against both doxorubicin and cisplatin compared with monolayer, adherent cells. In conclusion, sphere-forming cells with elevated ALDH1 are a possible candidate for sarcoma stem cells, possessing strong chemo-resistant capacities. Although ALDH1 elevation was not sufficient for representing sarcoma stem cells, the efficient detoxification could contribute to the chemo-resistant properties of the stem-like sphere cells form human sarcoma.