乳腺细胞肝酶通过MUC1/雌激素受体轴促进乳腺癌干状特征
Roberta Bongiorno1, Mara Lecchi2, Laura Botti1
1Molecular Immunology Unit, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milano, MI, Italy.
Cell death & disease
|September 30, 2024
概括
乳腺细胞通过肝酶活性和MUC1/雌激素受体信号传递促进乳腺癌干状特征. 这增强了瘤发育和他莫西芬耐药性,特别是在HER2-阴性乳腺癌亚型中.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 乳腺癌的异质性影响了结果.
- 免疫透,包括巨细胞,影响瘤的攻击性.
- 乳腺细胞在不同亚型的乳腺癌预后上表现出不同的影响.
研究的目的:
- 调查巨细胞在促进乳腺癌瘤发起性质方面的作用.
- 阐明巨细胞增强癌症干状特征的分子机制.
- 确定巨细胞活动对乳腺癌侵袭性和亚型特异性的影响.
主要方法:
- 同时注射巨细胞和癌细胞以评估体内移植.
- 涉及巨细胞肝酶和肝硫酸盐的分子通路的表征.
- 药理上抑制肝酶的作用.
- 分析巨细胞释放的可溶性因子及其对雌激素受体和MUC1表达的影响.
- 评估哺乳球的形成和干相关的基因表达.
- 在癌细胞中对他莫西芬敏感性的评估.
主要成果:
- 乳腺细胞显著增加癌细胞的体内移植率.
- 巨细胞肝酶活性和肝酸盐刺激对于促进瘤干状特征至关重要.
- 药理上抑制肝酶会废除由巨细胞介导的干细胞样性质的促进作用.
- 乳腺细胞释放的因子以MUC1依赖的方式诱导雌激素受体表达.
- MUC1/雌激素受体轴对于HER2-阴性细胞中癌症干细胞状特征至关重要,促进乳球形成和干基因表达.
- 这种机制降低了癌细胞对他莫西芬的敏感性.
结论:
- 乳腺细胞通过一种涉及肝酶和MUC1/雌激素受体轴的新机制促进乳腺癌的攻击性.
- 这一途径在HER2阴性乳腺癌中尤为重要,增强了干状特征和他莫西芬耐药性.
- 结果揭示了巨细胞介导的瘤促进中的亚型特异性差异,突出了一个新的治疗点.
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