Investigating the impact of the interstitial fluid flow and hypoxia interface on cancer transcriptomes using a spheroid-on-chip perfusion system,Lab on a Chip

当前位置： X-MOL 学术 › Lab Chip › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Investigating the impact of the interstitial fluid flow and hypoxia interface on cancer transcriptomes using a spheroid-on-chip perfusion system
Lab on a Chip ( IF 6.1 ) Pub Date : 2024-09-04 , DOI: 10.1039/d4lc00512k
Emily Pyne ₁ , Mark Reardon ₂ , Martin Christensen ₃ , Pablo Rodriguez Mateos ₄ , Scott Taylor ₅ , Alexander Iles ₄ , Ananya Choudhury _{2,

6} , Nicole Pamme ₄ , Isabel M Pires _{1,

5}

Affiliation

Solid tumours are complex and heterogeneous systems, which exist in a dynamic biophysical microenvironment. Conventional cancer research methods have long relied on two-dimensional (2D) static cultures which neglect the dynamic, three-dimensional (3D) nature of the biophysical tumour microenvironment (TME), especially the role and impact of interstitial fluid flow (IFF). To address this, we undertook a transcriptome-wide analysis of the impact of IFF-like perfusion flow using a spheroid-on-chip microfluidic platform, which allows 3D cancer spheroids to be integrated into extracellular matrices (ECM)-like hydrogels and exposed to continuous perfusion, to mimic IFF in the TME. Importantly, we have performed these studies both in experimental (normoxia) and pathophysiological (hypoxia) oxygen conditions. Our data indicated that gene expression was altered by flow when compared to static conditions, and for the first time showed that these gene expression patterns differed in different oxygen tensions, reflecting a differential role of spheroid perfusion in IFF-like flow in tumour-relevant hypoxic conditions in the biophysical TME. We were also able to identify factors primarily linked with IFF-like conditions which are linked with prognostic value in cancer patients and therefore could correspond to a potential novel biomarker of IFF in cancer. This study therefore highlights the need to consider relevant oxygen conditions when studying the impact of flow in cancer biology, as well as demonstrating the potential of microfluidic models of flow to identify IFF-relevant tumour biomarkers.

中文翻译：

使用球体芯片灌注系统研究间质液流动和缺氧界面对癌症转录组的影响

实体瘤是复杂且异质的系统，存在于动态的生物物理微环境中。传统的癌症研究方法长期以来依赖于二维（2D）静态培养，忽视了生物物理肿瘤微环境（TME）的动态、三维（3D）性质，特别是间质液流（IFF）的作用和影响。为了解决这个问题，我们使用片上球体微流体平台对类 IFF 灌注流的影响进行了全转录组分析，该平台允许将 3D 癌症球体整合到细胞外基质 (ECM) 类水凝胶中并暴露于连续灌注，模拟 TME 中的 IFF。重要的是，我们在实验（常氧）和病理生理（缺氧）氧条件下进行了这些研究。我们的数据表明，与静态条件相比，基因表达因流动而改变，并且首次表明这些基因表达模式在不同的氧张力下有所不同，反映了肿瘤相关缺氧中类 IFF 流动中球体灌注的不同作用生物物理 TME 中的条件。我们还能够确定主要与 IFF 样病症相关的因素，这些因素与癌症患者的预后价值相关，因此可能对应于癌症中 IFF 的潜在新型生物标志物。因此，本研究强调在研究流动对癌症生物学的影响时需要考虑相关的氧气条件，并证明流动微流体模型识别 IFF 相关肿瘤生物标志物的潜力。

更新日期：2024-09-04

点击分享查看原文

点击收藏

公开下载

阅读更多本刊新发论文本刊介绍/投稿指南