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在三维小鼠乳腺癌模型中,NK1受体阻断可破坏微肿瘤的生长和聚集。

NK1 receptor blockade disrupts microtumor growth and aggregation in a three-dimensional murine breast cancer model.

作者信息

Gutierrez Silvia, Boada M Danilo

机构信息

Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, NC, USA.

Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, NC, USA.

出版信息

Neuropeptides. 2025 Jan;109:102479. doi: 10.1016/j.npep.2024.102479. Epub 2024 Oct 16.

Abstract

Several data indicate that Substance P (SP) neurokinin type 1 receptor (NK1R) is at the center of the interaction between cancer cells and peripheral sensory neurons. Selecting the appropriate cancer cell line and its susceptibility to being modulated by NK1 antagonists are critical to studying this complex interaction. In the current study, we have focused on this selection by comparing several aspects of the triple-negative breast cancer (TNBC) cell line (MDA-MB-231) with a modified murine cell line (E0771), both expressing luciferase. This comparison was made using several methods, SP stimulation and 3D cell culture models, to better reproduce the heterogenous microenvironment of solid tumors observed in vivo. Furthermore, the susceptibility of the murine cell line (E0771) to NK1R antagonist (Aprepitant) was tested. Our results indicate that E0771 recapitulates several essential aspects of the human cell line, rendering this murine line ideal to be used on immune-competent animals during in vivo studies. We have also found that both cell lines are susceptible to SP stimulation, and their proliferation is disrupted by NK1R antagonists (Aprepitant). In vivo studies are required to verify and refine these findings.

摘要

多项数据表明,P物质(SP)神经激肽1型受体(NK1R)处于癌细胞与外周感觉神经元相互作用的核心。选择合适的癌细胞系及其对NK1拮抗剂调节的敏感性对于研究这种复杂的相互作用至关重要。在当前研究中,我们通过比较三阴性乳腺癌(TNBC)细胞系(MDA-MB-231)与改良的小鼠细胞系(E0771)的几个方面来专注于这种选择,这两种细胞系均表达荧光素酶。使用多种方法进行了这种比较,包括SP刺激和3D细胞培养模型,以更好地重现体内观察到的实体瘤的异质微环境。此外,还测试了小鼠细胞系(E0771)对NK1R拮抗剂(阿瑞匹坦)的敏感性。我们的结果表明,E0771概括了人类细胞系的几个基本方面,使该小鼠细胞系成为体内研究中用于免疫健全动物的理想选择。我们还发现,两种细胞系均对SP刺激敏感,并且它们的增殖被NK1R拮抗剂(阿瑞匹坦)破坏。需要进行体内研究来验证和完善这些发现。

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