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Updated: May 2, 2026
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A Combined 3D Tissue Engineered In Vitro/In Silico Lung Tumor Model for Predicting Drug Effectiveness in Specific Mutational Backgrounds
Published on: April 6, 2016
9.5K
Three-dimensional lung tumor microenvironment modulates therapeutic compound responsiveness in vitro--implication for
Jason E Ekert1, Kjell Johnson2, Brandy Strake1
1Biologics Research, Biotechnology Center of Excellence, Janssen R&D, LLC, Pharmaceutical Companies of Johnson & Johnson, Spring House, Pennsylvania, United States of America.
Plos One
|March 19, 2014
Summary
Three-dimensional (3D) spheroid cultures, unlike 2D monolayers, alter lung tumor cell responses to growth factors and targeted therapies, offering a more physiologically relevant model for cancer research.
Area of Science:
- Oncology
- Cell Biology
- Biotechnology
Background:
- Three-dimensional (3D) cell cultures, such as spheroids, are increasingly adopted for their ability to better replicate physiological tissue environments compared to traditional 2D monolayer cultures.
- Understanding the biological and functional differences between 3D spheroids and 2D monolayers is crucial for advancing cancer research and drug development.
Purpose of the Study:
- To characterize the phenotypic and functional disparities between lung tumor cells cultured as 3D spheroids versus 2D monolayers.
- To compare epidermal growth factor receptor (EGFR) and cMET expression, phosphorylation, and signaling pathway activation in both culture models.
Main Methods:
- Utilized eight lung tumor cell lines with varying EGFR and cMET expression to establish 3D spheroid models in low-attachment plates.
- Assessed EGFR and cMET expression and phosphorylation via flow cytometry and MSD assay, respectively.
- Evaluated cell proliferation, migration, and drug responsiveness to EGFR and cMET inhibitors (Erlotinib, Crizotinib, Cetuximab, Onartuzumab) in both 2D and 3D cultures.
Main Results:
- EGFR and cMET expression were reduced in untreated spheroid cultures by day four compared to monolayers.
- Basal phosphorylation of EGFR and cMET was higher in spheroids, while ligand-stimulated phosphorylation was reduced compared to 2D cultures.
- Spheroids exhibited altered proliferation responses to hepatocyte growth factor (HGF) and EGFR/cMET inhibitors, and demonstrated superior performance in cell migration assays.
Conclusions:
- 3D spheroid culture significantly modifies lung tumor cell responses to growth factors and targeted therapies.
- Spheroid models may provide a more accurate representation of the in vivo tumor microenvironment, impacting drug efficacy assessments.
- These findings highlight the importance of considering 3D culture systems for preclinical drug screening and understanding tumor biology.
