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Updated: May 16, 2026
Physiologic Patient Derived 3D Spheroids for Anti-neoplastic Drug Screening to Target Cancer Stem Cells
Published on: July 5, 2019
Screening therapeutic EMT blocking agents in a three-dimensional microenvironment
Amir R Aref1, Ruby Yun-Ju Huang, Weimiao Yu
1BioSystems and Micromechanics IRG, S16-07, SMART, Singapore 117543, Singapore.
Abstract:
Epithelial-mesenchymal transition (EMT) plays a critical role in the early stages of dissemination of carcinoma leading to metastatic tumors, which are responsible for over 90% of all cancer-related deaths. Current therapeutic regimens, however, have been ineffective in the cure of metastatic cancer, thus an urgent need exists to revisit existing protocols and to improve the efficacy of newly developed therapeutics. Strategies based on preventing EMT could potentially contribute to improving the outcome of advanced stage cancers. To achieve this goal new assays are needed to identify targeted drugs capable of interfering with EMT or to revert the mesenchymal-like phenotype of carcinoma to an epithelial-like state. Current assays are limited to examining the dispersion of carcinoma cells in isolation in conventional 2-dimensional (2D) microwell systems, an approach that fails to account for the 3-dimensional (3D) environment of the tumor or the essential interactions that occur with other nearby cell types in the tumor microenvironment. Here we present a microfluidic system that integrates tumor cell spheroids in a 3D hydrogel scaffold, in close co-culture with an endothelial monolayer. Drug candidates inhibiting receptor activation or signal transduction pathways implicated in EMT have been tested using dispersion of A549 lung adenocarcinoma cell spheroids as a metric of effectiveness. We demonstrate significant differences in response to drugs between 2D and 3D, and between monoculture and co-culture.
Insights
This study introduces a 3D microfluidic assay to better test drugs targeting epithelial-mesenchymal transition (EMT), a key process in cancer metastasis. The new system shows drug responses differ significantly from traditional 2D methods.
Area of Science:
- Oncology
- Biotechnology
- Cell Biology
Background:
- Epithelial-mesenchymal transition (EMT) is crucial for carcinoma cell dissemination and metastasis, a major cause of cancer mortality.
- Current therapies are ineffective against metastatic cancer, highlighting the need for improved therapeutic strategies and drug discovery methods.
- Existing assays for EMT lack 3D context and cell-cell interactions, limiting their predictive power for drug efficacy.
Purpose of the Study:
- To develop and validate a novel microfluidic assay for evaluating drugs targeting EMT.
- To assess the efficacy of drug candidates in a more biologically relevant 3D tumor microenvironment.
- To compare drug responses in 3D co-culture models versus traditional 2D monocultures.
Main Methods:
- A microfluidic system was designed to culture carcinoma cell spheroids within a 3D hydrogel scaffold.
- The 3D system integrated tumor spheroids in co-culture with an endothelial cell monolayer.
- Drug candidates targeting EMT pathways were tested, measuring the dispersion of A549 lung adenocarcinoma cell spheroids as a key metric.
Main Results:
- Significant differences in drug response were observed between 2D and 3D culture systems.
- Co-culture conditions in the 3D system revealed distinct drug efficacy compared to monocultures.
- The microfluidic assay effectively differentiated drug effects in a complex tumor microenvironment.
Conclusions:
- The developed 3D microfluidic co-culture system provides a more accurate platform for evaluating anti-metastatic drugs.
- This assay can aid in identifying targeted drugs that interfere with EMT or revert mesenchymal phenotypes.
- The findings underscore the importance of 3D and co-culture models for advancing cancer therapeutics.
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