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Multicellular Spheroids as a Model for Hypoxia-induced EMT.
Casey Lee1, Amanda Siu1, Daniel M Ramos2
1Department of Orofacial Sciences, University of California at San Francisco, San Francisco, CA, U.S.A.
Anticancer Research
|December 7, 2016
Summary
Oral cancer survival remains poor, with high recurrence rates. This study uses a multicellular spheroid model to investigate how the extracellular matrix and hypoxia drive oral squamous cell carcinoma (SCC) progression.
Area of Science:
- Oncology
- Biomedical Engineering
- Cancer Biology
Background:
- Oral cancer, specifically oral squamous cell carcinoma (SCC), is aggressive with a dismal 5-year survival rate of approximately 50%.
- Local and/or regional tumor recurrence affects one-third of oral cancer patients post-treatment, highlighting a critical unmet clinical need.
- Understanding the underlying mechanisms of SCC progression, including the roles of the tumor microenvironment, is crucial for developing novel therapeutic strategies.
Purpose of the Study:
- To investigate the contribution of the extracellular matrix (ECM) to epithelial to mesenchymal transition (EMT) in oral cancer.
- To elucidate the role of hypoxia in the progression of oral squamous cell carcinoma (SCC).
- To utilize a multicellular spheroid (MCS) model to simulate tumor microenvironment conditions and study SCC behavior.
Main Methods:
- Development and application of a multicellular spheroid (MCS) model to mimic the in vivo tumor microenvironment.
- Analysis of extracellular matrix (ECM) interactions and their influence on epithelial to mesenchymal transition (EMT) processes.
- Assessment of the impact of hypoxic conditions on the progression of oral squamous cell carcinoma (SCC) within the MCS model.
Main Results:
- The study identified specific ECM components and interactions that promote EMT in oral cancer cells.
- Hypoxia was demonstrated to significantly enhance SCC progression, likely through modulation of key signaling pathways.
- The MCS model proved effective in recapitulating key aspects of oral cancer aggressiveness and recurrence.
Conclusions:
- The extracellular matrix plays a significant role in driving epithelial to mesenchymal transition, a key event in oral cancer invasion and metastasis.
- Hypoxia is a critical factor contributing to the aggressive progression of oral squamous cell carcinoma (SCC).
- Further research utilizing the MCS model can provide deeper insights into oral cancer biology and inform the development of targeted therapies.
