在转移性内的伤口愈合程序的异常激活促进了骨髓瘤细胞的肺部殖民
James B Reinecke1,2, Leyre Jimenez Garcia3, Amy C Gross1
1Center for Childhood Cancer Research, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, Ohio.
概括
骨髓瘤肺转移是由纤维化驱动的. 抗纤维素药物宁泰丹尼布通过向瘤微环境,有效地阻止了这种进展,提供了一个新的治疗策略.
科学领域:
- 在瘤学瘤学.
- 肺部医学 肺部医学
- 翻译研究是翻译研究.
背景情况:
- 肺转移是骨髓瘤死亡的主要原因,骨髓瘤是一种常见的儿科骨癌.
- 骨髓瘤细胞为转移创造支持性肺微环境的机制尚未完全理解.
研究的目的:
- 为了确定特定于骨髓瘤转移的治疗脆弱性.
- 阐明骨髓瘤肺转移性利基形成的细胞和分子机制.
主要方法:
- 单细胞RNA测序和空间转录组学被用来分析来自小鼠模型和人类样本的肺组织中的分子变化.
- 多参数免疫光学证实了蛋白质水平上的转录组发现.
- 丁丁达尼布的疗效在骨髓瘤肺转移的小鼠和人类异种移植模型中进行了评估.
主要成果:
- 骨髓瘤细胞扩散诱导了急性膜上皮损伤和肺部肌层中慢性,不解决的伤口愈合表型.
- 与转移相关的肺部表现出显著的纤维化,这是由于益纤维的上皮细胞和巨细胞.
- 在临床前模型中,丁丁达尼布治疗抑制了骨髓瘤诱导的纤维化,并防止了转移性进展.
结论:
- 肺纤维化是骨髓瘤转移中的一个关键的,可针对性的漏洞.
- 骨髓瘤细胞和肺上皮细胞之间的相互作用通过细胞外基质沉积促进了前列腺转移的利基.
- 丁丁达尼布是一种氨酸激酶抑制剂,通过抑制纤维化来破坏这种利基,突出显示了TKI在转移中的非细胞自主作用.
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