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主要乳腺瘤诱导了前转移性肺部细胞外矩阵重塑

Ruoqing Cai¹, Caitlin M Tressler¹, Menglin Cheng¹

¹The Russell H. Morgan Department of Radiology and Radiological Science, Division of Cancer Imaging Research, The Johns Hopkins University School of Medicine, 720 Rutland Avenue, Traylor Building, Room 203, Baltimore, MD, 21205, USA.

Scientific reports

|October 31, 2023

概括

初级瘤通过改变细胞外基质 (ECM) 蛋白质,使肺微环境成为转移的首选. 这种先前转移的利基形成涉及原和矩阵金属蛋白酶的变化,促进癌细胞的扩散.

科学领域:

在瘤学瘤学.
细胞生物学细胞生物学
生物化学生物化学

背景情况:

前转移性利基假设表明,初级瘤积极为转移准备遥远的部位.
细胞外矩阵 (ECM) 改造对于这一过程至关重要,涉及结构性蛋白质和酶.

研究的目的:

为了研究ECM重塑在肺的前转移的利基.
为了确定由原发性乳腺瘤改变的特定的ECM蛋白和酶.

主要方法:

使用暴露于乳腺癌细胞因子的肺纤维细胞进行体外研究.
在体内研究评估ECM重塑在小鼠肺部与正确形状的乳腺瘤.
分析ECM结构蛋白,ECM降解酶和ECM加工蛋白.

主要成果:

前立腺癌肺部显示高调的原蛋白 (Col) Col4A5,矩阵金属蛋白酶 (MMPs) MMP9和MMP14,以及低调的MMP13和酸氧化酶 (LOX).
实验室发现证实了体内结果,转移性乳腺癌细胞介质改变了肺纤维细胞中的ECM蛋白,MMP和LOX水平.
具体的变化包括升高的Col14A1,Col4A5,glypican-1 (GPC1) 和增加的MMP2,MMP3,MMP14,以及降低的Col5A1,Col15A1,LOX,LOXL2和P4HA1.

结论:

原发性乳腺瘤诱导肺前转移性利基中显著的ECM重塑.
这种重塑,包括增加原和改变的MMPs,可能通过增加硬性,破坏底层膜,并促进泄漏的血管系统来促进转移.

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