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Updated: Apr 19, 2026
Tissue Engineering of Tumor Stromal Microenvironment with Application to Cancer Cell Invasion
Published on: March 18, 2014
Resolving cancer-stroma interfacial signalling and interventions with micropatterned tumour-stromal assays
Keyue Shen1, Samantha Luk1, Daniel F Hicks2
1Department of Surgery, Center for Engineering in Medicine and Surgical Services, Massachusetts General Hospital, Harvard Medical School and the Shriners Hospitals for Children, Boston, Massachusetts 02114, USA.
Abstract:
Tumour-stromal interactions are a determining factor in cancer progression. In vivo, the interaction interface is associated with spatially resolved distributions of cancer and stromal phenotypes. Here, we establish a micropatterned tumour-stromal assay (μTSA) with laser capture microdissection to control the location of co-cultured cells and analyse bulk and interfacial tumour-stromal signalling in driving cancer progression. μTSA reveals a spatial distribution of phenotypes in concordance with human oestrogen receptor-positive (ER+) breast cancer samples, and heterogeneous drug activity relative to the tumour-stroma interface. Specifically, an unknown mechanism of reversine is shown in targeting tumour-stromal interfacial interactions using ER+ MCF-7 breast cancer and bone marrow-derived stromal cells. Reversine suppresses MCF-7 tumour growth and bone metastasis in vivo by reducing tumour stromalization including collagen deposition and recruitment of activated stromal cells. This study advocates μTSA as a platform for studying tumour microenvironmental interactions and cancer field effects with applications in drug discovery and development.
Insights
This study introduces a new assay to study tumour-stromal interactions, revealing how reversine targets these interactions to suppress breast cancer growth and metastasis.
Area of Science:
- Oncology
- Cell Biology
- Biomedical Engineering
Background:
- Tumour-stromal interactions significantly influence cancer progression.
- The interface between tumour and stromal cells exhibits distinct spatial phenotypes.
- Understanding these interactions is crucial for developing effective cancer therapies.
Purpose of the Study:
- To develop a novel platform for analyzing tumour-stromal signaling.
- To investigate the role of spatial distribution in cancer progression and drug response.
- To explore the mechanism of reversine in targeting tumour-stromal interactions.
Main Methods:
- Establishment of a micropatterned tumour-stromal assay (μTSA).
- Utilizing laser capture microdissection for precise cell co-culture and analysis.
- In vivo and in vitro experiments with oestrogen receptor-positive (ER+) breast cancer cells and stromal cells.
Main Results:
- The μTSA platform accurately reflects spatial phenotype distribution observed in human breast cancer.
- Heterogeneous drug activity was observed at the tumour-stroma interface.
- Reversine demonstrated efficacy in suppressing tumour growth and bone metastasis by reducing stromalization.
Conclusions:
- The μTSA is a valuable platform for studying tumour microenvironmental interactions and cancer field effects.
- Reversine's mechanism involves targeting tumour-stromal interfacial interactions.
- This research has implications for drug discovery and development in cancer therapy.
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