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Updated: Nov 15, 2025
Quantitative and Temporal Control of Oxygen Microenvironment at the Single Islet Level
Published on: November 17, 2013
An Oxygen-Concentration-Controllable Multiorgan Microfluidic Platform for Studying Hypoxia-Induced Lung Cancer-Liver
Lulu Zheng1, Bo Wang1, Yunfan Sun2
1University of Shanghai for Science and Technology, 516 Jungong Road, Shanghai 200093, China.
Abstract:
Various cancer metastasis models based on organ-on-a-chip platforms have been established to study molecular mechanisms and screen drugs. However, current platforms can neither reveal hypoxia-induced cancer metastasis mechanisms nor allow drug screening under a hypoxia environment on a multiorgan level. We have developed a three-dimensional-culture multiorgan microfluidic (3D-CMOM) platform in which the dissolved oxygen concentration can be precisely controlled. An organ-level lung cancer and liver linkage model was established under normoxic/hypoxic conditions. A transcriptomics analysis of the hypoxia-induced lung cancer cells (A549 cells) on the platform indicated that the hypoxia-inducible factor 1α (HIF-1α) pathway could elevate epithelial-mesenchymal transition (EMT) transcription factors (Snail 1 and Snail 2), which could promote cancer metastasis. Then, protein detection demonstrated that HIF-1α and EMT transcription factor expression levels were positively correlated with the secretion of cancer metastasis damage factors alpha-fetoprotein (AFP), alkaline phosphatase (ALP), and gamma-glutamyl transpeptidase (γ-GT) from liver cells. Furthermore, the cancer treatment effects of HIF-1α inhibitors (tirapazamine, SYP-5, and IDF-11774) were evaluated using the platform. The treatment effect of SYP-5 was enhanced under the hypoxic conditions with fewer side effects, similar to the findings of TPZ. We can envision its wide application in future investigations of cancer metastasis and screening of drugs under hypoxic conditions with the potential to replace animal experiments.
Insights
This study introduces a novel multiorgan chip platform to model hypoxia-driven cancer metastasis and test drugs. It reveals the hypoxia-inducible factor 1α (HIF-1α) pathway promotes metastasis and identifies potential drug treatments.
Area of Science:
- Biomedical Engineering
- Cancer Research
- Microfluidics
Background:
- Organ-on-a-chip platforms are used for cancer metastasis research and drug screening.
- Existing platforms lack the ability to study hypoxia-induced metastasis or screen drugs in a hypoxic, multi-organ environment.
Purpose of the Study:
- To develop a 3D-culture multiorgan microfluidic (3D-CMOM) platform for controlled oxygen levels.
- To establish a lung cancer and liver model to investigate hypoxia-induced metastasis mechanisms.
- To evaluate drug efficacy under hypoxic conditions.
Main Methods:
- Development of a 3D-CMOM platform with precise dissolved oxygen control.
- Establishment of a lung cancer-liver organ linkage model under normoxic and hypoxic conditions.
- Transcriptomics and protein analysis to identify molecular pathways involved in metastasis.
- Evaluation of HIF-1α inhibitors for cancer treatment.
Main Results:
- Hypoxia-inducible factor 1α (HIF-1α) pathway activation promotes epithelial-mesenchymal transition (EMT) and cancer metastasis.
- HIF-1α and EMT transcription factors correlate with liver damage markers (AFP, ALP, γ-GT).
- SYP-5 demonstrated enhanced efficacy under hypoxia with reduced side effects, similar to tirapazamine (TPZ).
Conclusions:
- The 3D-CMOM platform effectively models hypoxia-induced cancer metastasis and drug screening.
- The HIF-1α/EMT pathway is crucial in hypoxia-driven lung cancer metastasis.
- This platform shows potential for replacing animal experiments in cancer research and drug development.
