Cancer stem-like properties of hormonal therapy-resistant breast cancer cells
Cancer stem-like properties of hormonal therapy-resistant breast cancer cells
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DOI：
10.1007/s12282-018-00944-1
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发表时间：
2019-01
期刊：
影响因子：
4
通讯作者：
Kanami Uchiumi;Kouki Tsuboi;Nozomi Sato;Takako Ito;H. Hirakawa;T. Niwa;Y. Yamaguchi;S. Hayashi
中科院分区：
文献类型：
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作者：
Kanami Uchiumi;Kouki Tsuboi;Nozomi Sato;Takako Ito;H. Hirakawa;T. Niwa;Y. Yamaguchi;S. Hayashi
背景目前，针对雌激素受体的激素治疗是治疗腔型乳腺癌最有效的治疗方法。然而，许多患者在治疗后复发。已经提出，癌症干细胞样细胞与激素治疗抗性有关;在本研究中，我们评估了这一假设。方法在本研究中，我们使用我们先前建立的激素治疗抗性细胞系，包括芳香化酶抑制剂（AI）抗性细胞（1型和2型）和氟维司群抗性细胞（MFR）。（1型V1和V2）在其CD 44/CD 24表达和侧群方面显示出较高的癌症干细胞性，这些细胞通过添加雌激素刺激并通过氟维司群抑制。然而，ALDH活性低于ER阴性耐药细胞，表明管腔细胞的干细胞性不同于基底样乳腺癌细胞。ER阳性的1型V1和V2细胞的迁移和侵袭活性高于ER阴性的细胞系，2型和MFR.ConclusionsFractionation的亲本细胞的基础上的CD 44/CD 24表达和集落形成试验表明，CD 44 +/CD 24+细胞可能是激素治疗耐药细胞的起源。这一群体在雌激素剥夺的情况下重建了各种其他亚群。这些结果表明，激素治疗抗性与管腔型乳腺癌的癌干细胞样性质密切相关。
BackgroundPresently, hormonal therapy targeting estrogen receptors is the most effective treatment available for luminal breast cancer. However, many patients relapse after the therapy. It has been suggested that cancer stem-like cells are involved with hormonal therapy resistance; in the present study, we evaluated this hypothesis.MethodsIn the present study, we used our previously established hormonal therapy-resistant cell lines, including aromatase inhibitor (AI)-resistant cells (Type 1 and Type 2) and fulvestrant-resistant cells (MFR).ResultsAI-resistant cell lines expressing ER (Type 1 V1 and V2) showed high cancer stemness in terms of their CD44/CD24 expression and side populations, which were stimulated by the addition of estrogen and inhibited by fulvestrant. However, ALDH activity was lower than in the ER-negative resistant cells, suggesting that the stemness of luminal cells is distinct from that of basal-like breast cancer cells. The migration and invasion activity of the ER-positive Type 1 V1 and V2 cells were higher than in the ER-negative cell lines, Type 2 and MFR.ConclusionsFractionation of parental cells based on CD44/CD24 expression and colony formation assay indicated that CD44+/CD24+ cells might be the origin of hormonal therapy-resistant cells. This population reconstituted various other subpopulations under estrogen deprivation. These results indicate that hormonal therapy resistance is closely related to the cancer stem cell-like properties of luminal breast cancer.