Journal
JOURNAL OF CELLULAR PHYSIOLOGY
Volume 234, Issue 4, Pages 3948-3960Publisher
WILEY
DOI: 10.1002/jcp.27209
Keywords
collagen; glioblastoma; hydrogel; inhibition; migration
Categories
Funding
- National Institute of General Medical Sciences [P20 GM103418]
- Wichita State University
- Wichita Medical Research and Education Foundation (WMREF)
- Flossie E. West Memorial Trust
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The invasion of glioblastoma is a complex process based on the interactions of tumor cells and the extracellular matrix. Tumors that are engineered using biomaterials are more physiologically relevant than a two-dimensional (2D) cell culture system. Matrix metalloproteinases and the plasminogen activator generated by tumor cells regulate a tumor's invasive behavior. In this study, microtumors were fabricated by encapsulating U87 glioma cells in Type I collagen and then glioma cell migration in the collagen hydrogels was investigated. Crosslinking of collagen with 8S-StarPEG increased the hydrogel viscosity and reduced the tumor cell migration speed in the hydrogels. The higher migration speed corresponded to the increased gene expression of MMP-2, MMP-9, urokinase plasminogen activator (uPA), and tissue plasminogen activator (tPA) in glioma cells grown in non-crosslinked collagen hydrogels. Inhibitors of these molecules hindered U87 and A172 cell migration in collagen hydrogels. Aprotinin and tranexamic acid did not inhibit U87 and A172 migration on the culture dish. This study demonstrated the differential effect of pharmacologic molecules on tumor cell motility in either a 2D or three-dimensional culture environment.
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