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Updated: Dec 8, 2025
Three-Dimensional Culture Assay to Explore Cancer Cell Invasiveness and Satellite Tumor Formation
Published on: August 18, 2016
3D Bone Morphology Alters Gene Expression, Motility, and Drug Responses in Bone Metastatic Tumor Cells
Ushashi C Dadwal1,2,3, Alyssa R Merkel1,3,4, Jonathan M Page2
1Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN 37212, USA.
Abstract:
Patients with advanced skeletal metastases arising from primary cancers including breast, lung, and prostate suffer from extreme pain, bone loss, and frequent fractures. While the importance of interactions between bone and tumors is well-established, our understanding of complex cell-cell and cell-microenvironment interactions remains limited in part due to a lack of appropriate 3D bone models. To improve our understanding of the influence of bone morphometric properties on the regulation of tumor-induced bone disease (TIBD), we utilized bone-like 3D scaffolds in vitro and in vivo. Scaffolds were seeded with tumor cells, and changes in cell motility, proliferation, and gene expression were measured. Genes associated with TIBD significantly increased with increasing scaffold rigidity. Drug response differed when tumors were cultured in 3D compared to 2D. Inhibitors for Integrin β3 and TGF-β Receptor II significantly reduced bone-metastatic gene expression in 2D but not 3D, while treatment with the Gli antagonist GANT58 significantly reduced gene expression in both 2D and 3D. When tumor-seeded 3D scaffolds were implanted into mice, infiltration of myeloid progenitors changed in response to pore size and rigidity. This study demonstrates a versatile 3D model of bone used to study the influence of mechanical and morphometric properties of bone on TIBD.
Insights
This study introduces a novel 3D bone model to investigate tumor-induced bone disease (TIBD). The model reveals how bone properties influence cancer cell behavior and drug response, advancing TIBD research.
Area of Science:
- Biomedical Engineering
- Oncology
- Skeletal Biology
Background:
- Skeletal metastases cause severe pain and fractures in cancer patients.
- Current understanding of tumor-bone interactions is limited by a lack of advanced 3D models.
- Investigating the bone microenvironment is crucial for understanding tumor-induced bone disease (TIBD).
Purpose of the Study:
- To develop and utilize a 3D bone scaffold model to study the influence of bone morphometric properties on TIBD.
- To assess how scaffold rigidity and other properties affect tumor cell behavior and gene expression.
- To compare drug efficacy in 3D versus 2D tumor models.
Main Methods:
- Development of bone-like 3D scaffolds for in vitro and in vivo studies.
- Seeding scaffolds with tumor cells and measuring changes in cell motility, proliferation, and gene expression.
- Implanting tumor-seeded 3D scaffolds in mice to observe myeloid progenitor infiltration.
Main Results:
- Increased scaffold rigidity correlated with elevated TIBD-associated gene expression.
- Drug responses varied significantly between 3D and 2D culture models.
- Specific drug inhibitors showed differential efficacy based on dimensionality.
- Tumor-seeded scaffolds in mice demonstrated altered myeloid progenitor infiltration based on scaffold properties.
Conclusions:
- The developed 3D bone model is a versatile tool for studying TIBD.
- Bone morphometric properties significantly influence tumor cell behavior and drug response in TIBD.
- This model provides new insights into the complex interactions within the bone metastatic niche.
