ECM-Integrated Hanging Drop Platform for Spatially Controlled Assessment of Immune Cell Regulated Tumour Invasion

IF 5.4 2区 工程技术 Q1 BIOCHEMICAL RESEARCH METHODS
Lab on a Chip Pub Date : 2025-09-22 DOI:10.1039/d5lc00359h
Sungsu Park, Chanyang Lee, Seokgyu Han, Seulgi Lee, Jaehyun Lee, Sein Kim, Seunggyu Ko, Howon Lee
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引用次数: 0

Abstract

The tumour immune microenvironment (TIME) plays a crucial role in tumour progression and metastasis. Although spheroids effectively model tumour invasion by mimicking in vivo 3D structures, their formation and subsequent mixing with the matrix make it difficult to control their position in the 3D matrix, leading to deep embedding and hindering the assessment of immune cell-mediated regulation of invasion. This paper introduces an extracellular matrix (ECM)-integrated hanging drop platform that enables simultaneous spheroid formation and matrix incorporation, allowing precise spatial control and direct assessment of immune cell- mediated regulation of invasion. In the presence of microglia (MG), cancer cells rapidly migrate out of the spheroids through the ECM, demonstrating cancer invasion. The cytotoxic effect of natural killer (NK) cells on glioblastoma multiforme (GBM) spheroids is decreased owing to the inhibition of NK cell infiltration in the presence of MG, highlighting the immunosuppressive nature of the TIME. However, inhibiting STAT3 activation with drugs halts MG-induced immunosuppression and enhances NK cell infiltration. This model enables efficient high-throughput screening and is the first to allow for precise quantification of the effects of the STAT3 inhibitor on tumour invasion, immune cell movement, and behaviour within a physiologically relevant GBM TIME model.
免疫细胞调节肿瘤侵袭的空间控制评估- ecm集成悬滴平台
肿瘤免疫微环境(TIME)在肿瘤的进展和转移中起着至关重要的作用。虽然球体通过模拟体内三维结构有效地模拟肿瘤侵袭,但它们的形成以及随后与基质的混合使得它们在三维基质中的位置难以控制,从而导致深度嵌入,阻碍了免疫细胞介导的侵袭调节的评估。本文介绍了一种细胞外基质(ECM)集成悬滴平台,该平台可以同时形成球体和结合基质,从而实现精确的空间控制和直接评估免疫细胞介导的入侵调节。在小胶质细胞(MG)存在的情况下,癌细胞通过ECM迅速迁移出球体,表明癌症侵袭。自然杀伤(NK)细胞对多形胶质母细胞瘤(GBM)球体的细胞毒性作用由于MG存在时抑制NK细胞浸润而降低,突出了TIME的免疫抑制性质。然而,用药物抑制STAT3的激活可以停止mg诱导的免疫抑制并增强NK细胞的浸润。该模型实现了高效的高通量筛选,并且是第一个允许在生理相关的GBM TIME模型中精确量化STAT3抑制剂对肿瘤侵袭、免疫细胞运动和行为的影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Lab on a Chip
Lab on a Chip 工程技术-化学综合
CiteScore
11.10
自引率
8.20%
发文量
434
审稿时长
2.6 months
期刊介绍: Lab on a Chip is the premiere journal that publishes cutting-edge research in the field of miniaturization. By their very nature, microfluidic/nanofluidic/miniaturized systems are at the intersection of disciplines, spanning fundamental research to high-end application, which is reflected by the broad readership of the journal. Lab on a Chip publishes two types of papers on original research: full-length research papers and communications. Papers should demonstrate innovations, which can come from technical advancements or applications addressing pressing needs in globally important areas. The journal also publishes Comments, Reviews, and Perspectives.
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