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Generation of 3D Tumor Spheroids for Drug Evaluation Studies
Published on: February 24, 2023
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3D microengineered vascularized tumor spheroids for drug delivery and efficacy testing
Jungho Ahn1, Da-Hyun Kim2, Dong-Jun Koo3
1Department of Mechanical and Aerospace Engineering, Seoul National University, Seoul 08826, Republic of Korea; George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
Acta Biomaterialia
|October 15, 2022
Summary
Researchers developed a vascularized tumor spheroid (VTS) model using hybrid tumor-endothelial cells. This model accurately mimics tumor features, aiding in understanding cancer progression and testing drug efficacy against tumor growth and angiogenesis.
Area of Science:
- Oncology
- Biomedical Engineering
- Cancer Research
Background:
- Tumor angiogenesis is crucial for cancer progression, supplying nutrients and enabling metastasis.
- In vitro models are needed to study tumor cell behavior and drug responses.
- Understanding tumor microenvironments is key for developing effective cancer therapies.
Purpose of the Study:
- To develop a microengineered vascularized tumor spheroid (VTS) model for studying solid tumor pathology.
- To investigate the role of tumor vascularization in cancer progression and drug efficacy.
- To explore therapeutic strategies targeting tumor microenvironments.
Main Methods:
- Microengineering of tumor-endothelial cell (EC) hybrid spheroids to create intratumoral vessels.
- Utilizing the VTS chip to observe peritumoral angiogenesis and vessel characteristics.
- Employing RNA sequencing to analyze gene expression profiles of hybrid spheroids.
- Validating drug efficacy (axitinib) on tumor growth and angiogenesis within the VTS model.
- Inducing lymphangiogenesis and angiogenesis by promoting interstitial flow.
Main Results:
- Hybrid tumor-EC spheroids showed enhanced uniformity and angiogenic capacity compared to cancer cell-only spheroids.
- RNA sequencing revealed expression profiles linked to aggressive cancer behaviors like invasion and metastasis.
- Sprouting blood vessels mimicked leaky tumor vasculature.
- Axitinib demonstrated dose- and time-dependent suppression of tumor growth and angiogenesis.
- Interstitial flow successfully induced both lymphangiogenesis and angiogenesis.
Conclusions:
- The VTS model effectively recapitulates key pathological features of solid tumors, including vascularization and aggressive behavior.
- The model serves as a valuable platform for investigating tumor microenvironment interactions.
- The VTS model can predict the efficacy of anti-cancer drugs by assessing their impact on tumor vascularization.
- This platform facilitates the exploration of novel therapeutic strategies for cancer treatment.
