肺赖氨酸氧化酶在Lewis肺癌细胞中的表达及其作用。

IF 4.2 3区 医学 Q2 ONCOLOGY
Kimberly J Jasmer, Vinit C Shanbhag, Kevin Muñoz Forti, Lucas T Woods, Nikita S Gudekar, Gary A Weisman, Michael J Petris
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引用次数: 0

摘要

铜通过多种机制促进肿瘤生长和转移,最显著的是作为分泌的铜原酶赖氨酸氧化酶(LOX)家族中的辅助因子。该家族的成员,包括LOX和LOX样酶LOXL1-4,在细胞外基质(ECM)中催化胶原和弹性蛋白的铜依赖性交联。在包括结直肠癌、乳腺癌、胰腺癌和头颈部在内的多种癌症中,LOX表达升高与更高的发病率和更差的预后相关。在这项研究中,我们证明了LOX表达升高与肺癌患者总生存期下降和首次进展的中位时间缩短相关。先前的研究表明,肿瘤分泌的LOX通过促进ECM重塑和免疫细胞和内皮前体的募集,对转移前生态位的形成至关重要。在这里,我们证明了在同基因小鼠模型中,与野生型LLC细胞相比,Lewis肺癌(LLC)细胞中LOX基因的消融减少了肿瘤的生长和转移。虽然肿瘤来源的LOX在肿瘤形成和转移中的作用已经得到了很好的证实,但对于转移器官实质组织产生的LOX的可能贡献知之甚少。因此,本报告描述了我们的发现,即肺产生的宿主来源的LOX有助于小鼠LLC细胞的肺转移。肺赖氨酸氧化酶表达的抑制降低了小鼠Lewis肺癌细胞的转移潜能,揭示了转移靶器官实质组织中LOX表达对肿瘤细胞播散的未知影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Pulmonary lysyl oxidase expression and its role in seeding Lewis lung carcinoma cells.

Copper promotes tumor growth and metastasis through a variety of mechanisms, most notably as a cofactor within the lysyl oxidase (LOX) family of secreted cuproenzymes. Members of this family, which include LOX and LOX-like enzymes LOXL1-4, catalyze the copper-dependent crosslinking of collagens and elastin within the extracellular matrix (ECM). Elevated LOX expression is associated with higher incidence and worse prognosis in multiple cancers, including colorectal, breast, pancreatic, and head and neck. In this study, we demonstrated that elevated LOX expression correlates with decreased overall survival and shorter median time to first progression in patients with lung cancer. Previous studies have demonstrated that LOX secreted from tumors is critical for pre-metastatic niche formation by promoting ECM remodeling and the recruitment of immune cells and endothelial precursors. Here, we demonstrated that ablation of the LOX gene in Lewis lung carcinoma (LLC) cells diminishes tumor growth and metastasis compared to wild-type LLC cells in a syngeneic mouse model. Although the role of tumor-derived LOX in tumor formation and metastasis is well established, little is known regarding the possible contribution of LOX produced by the parenchymal tissue of metastatic organs. Thus, this report describes our findings that host-derived LOX produced by the lung contributes to the pulmonary metastasis of LLC cells in mice. The suppression of pulmonary lysyl oxidase expression reduces the metastatic potential of Lewis Lung Carcinoma cells in mice, revealing a previously unknown influence of LOX expression in the parenchymal tissue of metastatic target organs on the seeding of tumor cells.

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来源期刊
CiteScore
7.80
自引率
5.00%
发文量
55
审稿时长
12 months
期刊介绍: The Journal''s scope encompasses all aspects of metastasis research, whether laboratory-based, experimental or clinical and therapeutic. It covers such areas as molecular biology, pharmacology, tumor biology, and clinical cancer treatment (with all its subdivisions of surgery, chemotherapy and radio-therapy as well as pathology and epidemiology) insofar as these disciplines are concerned with the Journal''s core subject of metastasis formation, prevention and treatment.
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