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

IF 2.5 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

Neuropeptides Pub Date : 2024-10-16 DOI:10.1016/j.npep.2024.102479

Silvia Gutierrez, M. Danilo Boada

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引用次数: 0

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^LUC+) with a modified murine cell line (E0771^LUC+), 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^LUC+) to NK1R antagonist (Aprepitant) was tested. Our results indicate that E0771^LUC+ 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.

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阻断 NK1 受体可破坏三维鼠乳腺癌模型中微肿瘤的生长和聚集

一些数据表明，P 物质（SP）神经激肽 1 型受体（NK1R）是癌细胞与外周感觉神经元之间相互作用的中心。选择合适的癌细胞系及其对 NK1 拮抗剂的敏感性是研究这种复杂相互作用的关键。在目前的研究中，我们通过比较三阴性乳腺癌（TNBC）细胞系（MDA-MB-231LUC+）和改良鼠细胞系（E0771LUC+）的几个方面，重点研究了这一选择问题。这种比较采用了多种方法，包括 SP 刺激和三维细胞培养模型，以更好地再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（E0771LUC+）对 NK1R 拮抗剂（Aprepitant）的敏感性。我们的研究结果表明，E0771LUC+ 重现了人类细胞系的几个重要方面，因此这种鼠细胞系非常适合在体内研究中用于免疫功能正常的动物。我们还发现，这两种细胞系都易受 SP 刺激，NK1R 拮抗剂（Aprepitant）会破坏它们的增殖。要验证和完善这些发现，还需要进行体内研究。

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来源期刊

Neuropeptides 医学-内分泌学与代谢

CiteScore

5.40

自引率

6.90%

发文量

审稿时长

>12 weeks

期刊介绍： The aim of Neuropeptides is the rapid publication of original research and review articles, dealing with the structure, distribution, actions and functions of peptides in the central and peripheral nervous systems. The explosion of research activity in this field has led to the identification of numerous naturally occurring endogenous peptides which act as neurotransmitters, neuromodulators, or trophic factors, to mediate nervous system functions. Increasing numbers of non-peptide ligands of neuropeptide receptors have been developed, which act as agonists or antagonists in peptidergic systems. The journal provides a unique opportunity of integrating the many disciplines involved in all neuropeptide research. The journal publishes articles on all aspects of the neuropeptide field, with particular emphasis on gene regulation of peptide expression, peptide receptor subtypes, transgenic and knockout mice with mutations in genes for neuropeptides and peptide receptors, neuroanatomy, physiology, behaviour, neurotrophic factors, preclinical drug evaluation, clinical studies, and clinical trials.