通过自漂浮细胞培养揭示的乳腺癌细胞动态表型转变
Dynamic Phenotypic Transition of Breast Cancer Cells Revealed by Self-floating Cell Culture.
作者信息
Oku Yusuke, Nishiya Naoyuki, Tsuda Kayoko, Shibazaki Masahiko, Maesawa Chihaya, Uehara Yoshimasa
机构信息
Departments of Integrated Information for Pharmaceutical Sciences, Iwate Medical University School of Pharmacy, Iwate, Japan
Departments of Integrated Information for Pharmaceutical Sciences, Iwate Medical University School of Pharmacy, Iwate, Japan.
出版信息
Anticancer Res. 2017 Apr;37(4):1793-1797. doi: 10.21873/anticanres.11513.
BACKGROUND
Breast tumor heterogeneity leads to phenotypic diversity, such as tumor-initiating and metastatic properties and drug sensitivity.
MATERIALS AND METHODS
We found that a self-floating cell (SFC) culture enriches a drug-resistant subpopulation in a HER2-positive breast cancer cell line. SFCs were analyzed for cancer stem cell markers, gene expression profiles, and sensitivity for anticancer drugs.
RESULTS
SFCs expressed cancer stem cell markers, such as aldehyde dehydrogenase (ALDH) activity and elevated HER2 autophosphorylation. Gene expression profiles of SFCs showed a dramatic difference compared to those of parental or forced floating cells. SFCs also expressed CD133, a marker of drug resistance, and resisted cytotoxic drugs by drug efflux transporters. In contrast, HER2 kinase inhibitors efficiently reduced SFC viability.
CONCLUSION
SFCs enrich drug-resistant subpopulations even in vitro and might reflect the highly plastic nature of breast cancer cells even in vitro.
背景
乳腺肿瘤异质性导致表型多样性，如肿瘤起始和转移特性以及药物敏感性。
材料与方法
我们发现一种自漂浮细胞（SFC）培养可富集HER2阳性乳腺癌细胞系中的耐药亚群。对SFC进行癌症干细胞标志物、基因表达谱及抗癌药物敏感性分析。
结果
SFC表达癌症干细胞标志物，如醛脱氢酶（ALDH）活性及HER2自磷酸化水平升高。与亲本细胞或强制漂浮细胞相比，SFC的基因表达谱显示出显著差异。SFC还表达耐药标志物CD133，并通过药物外排转运体抵抗细胞毒性药物。相比之下，HER2激酶抑制剂可有效降低SFC活力。
结论
即使在体外，SFC也能富集耐药亚群，甚至可能反映乳腺癌细胞在体外的高度可塑性。
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