Sungsu Park, Chanyang Lee, Seokgyu Han, Seulgi Lee, Jaehyun Lee, Sein Kim, Seunggyu Ko, Howon Lee
{"title":"ECM-Integrated Hanging Drop Platform for Spatially Controlled Assessment of Immune Cell Regulated Tumour Invasion","authors":"Sungsu Park, Chanyang Lee, Seokgyu Han, Seulgi Lee, Jaehyun Lee, Sein Kim, Seunggyu Ko, Howon Lee","doi":"10.1039/d5lc00359h","DOIUrl":null,"url":null,"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.","PeriodicalId":85,"journal":{"name":"Lab on a Chip","volume":"79 1","pages":""},"PeriodicalIF":5.4000,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Lab on a Chip","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1039/d5lc00359h","RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
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.
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.