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Updated: Jul 25, 2025
Spheroid Assay to Measure TGF-β-induced Invasion
Published on: November 16, 2011
An agarose-alginate microfluidic device for the study of spheroid invasion, ATRA inhibits CAFs-mediated matrix
Mohammad Reza Nasiraee1, Shabnam Shahrivari1, Soheila Sayad2
1Department of Medical Biotechnology, Faculty of Allied Medical Sciences, Iran University of Medical Sciences, Tehran 1449614535, Iran.
Abstract:
Growing evidence demonstrates that cancer-associated fibroblasts (CAF) are responsible for tumor genesis, growth, metastasis, and treatment response. Therefore, targeting these cells may contribute to tumor control. It has been proposed that targeting key molecules and pathways of proliferative functions can be more effective than killing CAFs. In this regard, multicellular aggregates, like spheroids, can be used as human tumor models. Spheroids closely resemble human tumors and mimic many of their features. Microfluidic systems are ideal for cultivation and study of spheroids. These systems can be designed with different biological and synthetic matrices in order to have a more realistic simulation of the tumor microenvironment (TME). In this study, we investigated the effect of all-trans retinoic acid (ATRA) on 3D spheroid invasion of MDA-MB cells exposed to hydrogel matrix derived from CAFs. The number of invasive cells significantly decreased in CAF-ECM hydrogel treated with ATRA (p < 0.05), which indicates that ATRA could be effective for CAFs normalization. This experiment was done using an agarose-alginate microfluidic chip. As compared with common methods, such hydrogel casting is an easier method for chip fabrication and can even reduce costs.
Supplementary Information:
The online version contains supplementary material available at 10.1007/s10616-023-00578-y.
Insights
All-trans retinoic acid (ATRA) effectively normalized cancer-associated fibroblast (CAF) functions in a 3D tumor model. ATRA reduced cancer cell invasion within CAF-derived matrices, suggesting a therapeutic strategy for normalizing CAFs.
Area of Science:
- Oncology
- Biomaterials Science
- Cancer Biology
Background:
- Cancer-associated fibroblasts (CAFs) drive tumor progression, metastasis, and treatment resistance.
- Targeting CAF proliferative functions offers a potential therapeutic strategy for cancer control.
- Multicellular spheroids within microfluidic systems provide realistic tumor microenvironment (TME) models.
Purpose of the Study:
- To investigate the effect of all-trans retinoic acid (ATRA) on 3D spheroid invasion within a CAF-derived extracellular matrix (ECM) hydrogel.
- To evaluate ATRA's potential for normalizing CAF functions in a tumor model.
- To assess the utility of microfluidic systems with CAF-ECM hydrogels for studying anti-cancer agents.
Main Methods:
- Utilized an agarose-alginate microfluidic chip for spheroid culture.
- Incorporated CAF-derived ECM into a hydrogel matrix to simulate the TME.
- Exposed MDA-MB cell spheroids within the CAF-ECM hydrogel to all-trans retinoic acid (ATRA).
Main Results:
- ATRA treatment significantly reduced the number of invasive cells in the CAF-ECM hydrogel (p < 0.05).
- This reduction indicates a potential for ATRA to normalize CAF behavior.
- The hydrogel casting method proved simpler and more cost-effective for chip fabrication.
Conclusions:
- All-trans retinoic acid (ATRA) demonstrates efficacy in normalizing cancer-associated fibroblast (CAF) functions within a 3D tumor model.
- ATRA treatment reduces cancer cell invasion, highlighting its therapeutic potential.
- Microfluidic systems with CAF-ECM hydrogels offer a viable and cost-effective platform for evaluating anti-cancer therapies targeting CAFs.
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