三维模型分析揭示了 NK-92 细胞系和原代 NK 细胞对乳腺癌和卵巢癌细胞系的不同细胞毒性作用,这种作用是由受体-配体相互作用和可溶性因子谱的变化介导的。

IF 3.9 3区 工程技术 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Biomedicines Pub Date : 2024-10-20 DOI:10.3390/biomedicines12102398
Nadezhda A Alekseeva, Anna A Boyko, Marina A Shevchenko, Maria V Grechikhina, Maria A Streltsova, Ludmila G Alekseeva, Alexander M Sapozhnikov, Sergey M Deyev, Elena I Kovalenko
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引用次数: 0

摘要

背景/目的:某种肿瘤的功能活性决定了原代 NK 细胞和 NK-92 细胞系的癌症治疗效果;它们对不同肿瘤的治疗效果也会不同。本研究直接同时比较了体外激活的外周 NK(pNK)细胞和 NK-92 细胞在 BT-474、MCF7 和 SKOV-3 癌症球状模型中的细胞毒性作用,并揭示了 NK 细胞对肿瘤的不同疗效的原因。研究方法用流式细胞术或共聚焦显微镜检测肿瘤细胞的死亡。进行细胞因子产生、颗粒酶 B 水平和 NK 细胞脱颗粒分析,以及 pNK 和靶细胞表型鉴定。结果:虽然 NK-92 和 pNK 细胞裂解 BT-474 球形细胞的效率相当低,但 pNK 细胞比 NK-92 细胞更能消除 MCF7 和 SKOV-3 球形细胞。功能和表型分析结果强烈支持 NKG2D-NKG2DL 通路参与了对 SKOV-3 球形体最敏感的细胞毒性攻击所诱导的 pNK 细胞活化,而 CX3CR1-CX3CL1 轴似乎参与了 pNK 对 MCF-7 球形体的反应。结论:我们提供了一种新方法来初步鉴定最有前途的 NK 细胞受体,这些受体可根据特定的肿瘤类型改变癌症治疗的效果。利用这种方法,可以选择 NK-92 细胞或 pNK 亚群进行进一步积累和/或基因修饰,以提高特异性和反应性。
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Three-Dimensional Model Analysis Revealed Differential Cytotoxic Effects of the NK-92 Cell Line and Primary NK Cells on Breast and Ovarian Carcinoma Cell Lines Mediated by Variations in Receptor-Ligand Interactions and Soluble Factor Profiles.

Background/objectives: The functional activity of a certain tumor determines the effectiveness of primary NK cells and NK-92 cell line-based cancer therapy; their therapeutic effectiveness against different tumors can vary. This work provides a direct simultaneous comparison of the cytotoxic effects of in vitro-activated peripheral NK (pNK) cells and NK-92 cells in spheroid models of BT-474, MCF7 and SKOV-3 carcinomas and uncovers the reasons for the differential effectiveness of NK cells against tumors. Methods: Tumor spheroids of similar size and shape, obtained from agarose molds, were incubated with NK-92 or pNK cells for 24 h. Tumor cell death was detected using flow cytometry or confocal microscopy. Cytokine production, granzyme B levels and NK cell degranulation analyses were performed, along with pNK and target-cell phenotypic characterization. Results: While NK-92 and pNK cells lysed BT-474 spheroids with comparably low efficiency, pNK cells were more capable of eliminating MCF7 and SKOV-3 spheroids than NK-92 cells were. The results of the functional and phenotypic analyses strongly support the participation of the NKG2D-NKG2DL pathway in pNK cell activation induced by the most sensitive cytotoxic attack on SKOV-3 spheroids, whereas the CX3CR1-CX3CL1 axis appears to be involved in the pNK reaction against MCF-7 spheroids. Conclusions: We provide a new approach for the preliminary identification of the most promising NK cell receptors that can alter the effectiveness of cancer therapy depending on the specific tumor type. Using this approach, NK-92 cells or pNK subsets can be selected for further accumulation and/or genetic modification to improve specificity and reactivity.

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来源期刊
Biomedicines
Biomedicines Biochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology
CiteScore
5.20
自引率
8.50%
发文量
2823
审稿时长
8 weeks
期刊介绍: Biomedicines (ISSN 2227-9059; CODEN: BIOMID) is an international, scientific, open access journal on biomedicines published quarterly online by MDPI.
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