Departmental Papers (Dental)
A Novel 3-Dimensional Culture System as an In Vitro Model for Studying Oral Cancer Cell Invasion
Date of this Version
International Journal of Experimental Pathology
Tissue microenvironment plays a critical role in tumour growth and invasion. This study established a novel 3-dimensional (3-D) cell invasion model for direct microscopic observation of oral cancer cell invasion into the underlying basement membrane and connective tissue stroma. A multilayer cell construct was developed using the OptiCell chamber, consisting of a lower layer of oral mucosa fibroblasts embedded in collagen gel and an overlaying upper layer of oral cancer cells. The two layers are separated by a basement membrane composed of reconstituted extracellular matrix. To verify the applicability of the cell invasion model, multilayer cell constructs of oral squamous cell carcinoma and oral mucosal fibroblasts were exposed to extrinsic urokinase-type plasminogen activator (uPA) or plasminogen activator inhibitor (PAI-1), which are known effectors of cell migration. In addition, the constructs were exposed to both normoxic and hypoxic culture conditions. Microscopic study showed that the presence of uPA enhanced cell invasion, while PAI-1 inhibited cell migration. Western blot and zymographic analysis demonstrated that hypoxia up-regulated uPA and matrix metalloproteinases (MMPs) expression and activity; conversely, PAI-1 level was down-regulated in response to hypoxic challenge as compared to normoxic condition. Our results indicated that the novel 3-D invasion model could serve as an excellent in vitro model to study cancer cell invasion and to test conditions or mediators of cellular migration. © 2005 Blackwell Publishing Ltd.
3-D construct, Hypoxia, Opticell chamber, Oral cancer invasion, Blotting, Western, Cell Hypoxia, Coculture Techniques, Electrophoresis, Polyacrylamide Gel, Fibroblasts, Humans, Mouth Mucosa, Mouth Neoplasms, Neoplasm Invasiveness, Plasminogen Activator Inhibitor 1, Urinary Plasminogen Activator, plasminogen activator inhibitor, urokinase receptor, article, cancer cell culture, cancer invasion, cell invasion, cell migration, controlled study, down regulation, enzyme activity, fibroblast, human, human cell, hypoxia, microscopy, mouth cancer, priority journal, protein expression, Western blotting, zymography
Duong, H. S., Le, A. D., Zhang, Q., & Messadi, D. V. (2005). A Novel 3-Dimensional Culture System as an In Vitro Model for Studying Oral Cancer Cell Invasion. International Journal of Experimental Pathology, 86 (6), 365-374. http://dx.doi.org/10.1111/j.0959-9673.2005.00441.x
Date Posted: 10 February 2023
This document has been peer reviewed.
At the time of publication, author Anh D. Le was affiliated with the University of Southern California, School of Dentistry and Jonsson Comprehensive Cancer Center. Currently, (s)he is a faculty member at the School of Medical Dentistry at the University of Pennsylvania.
At the time of publication, author Qunzhou Zhang was affiliated with the University of Southern California, School of Dentistry. Currently, (s)he is a faculty member at the School of Medical Dentistry at the University of Pennsylvania.