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Sarkar, Susobhan, Nuttall, Robert K., Liu, Shuhong, Edwards, Dylan R. 
ORCID: https://orcid.org/0000-0002-3292-2064 and Yong, V. Wee
(2006)
Tenascin-C stimulates glioma cell invasion through matrix metalloproteinase-12.
Cancer Research, 66 (24).
pp. 11771-11780.
Abstract
The capacity of glioma cells to invade extensively within the central nervous system is a major cause of the high morbidity rate of primary malignant brain tumors. Glioma cell invasion involves the attachment of tumor cells to extracellular matrix (ECM), degradation of ECM components, and subsequent penetration into adjacent brain structures. These processes are accomplished in part by matrix metalloproteinases (MMP) within a three-dimensional milieu of the brain parenchyma. As the majority of studies have used a two-dimensional monolayer culture system, we have used a three-dimensional matrix of collagen type I gel to address glioma-secreted proteases, ECM, and invasiveness of glioma cells. We show that in a three-dimensional collagen type I matrix, the presence of tenascin-C, commonly elevated in high-grade gliomas, increased the invasiveness of glioma cells. The tenascin-C–mediated invasiveness was blocked by metalloproteinase inhibitors, but this did not involve the gelatinases (MMP-2 and MMP-9) commonly implicated in two-dimensional glioma growth. A thorough analysis of 21 MMPs and six members of a disintegrin and metalloproteinase domain showed that MMP-12 was increased in gliomas by tenascin-C in three-dimensional matrix. Furthermore, examinations of resected specimens revealed high MMP-12 levels in the high-grade glioblastoma multiforme tumors. Finally, a function-blocking antibody as well as small interfering RNA to MMP-12 attenuated the tenascin-C–stimulated glioma invasion. These results identify a new factor, MMP-12, in regulating glioma invasiveness through interaction with tenascin-C.
| Item Type: | Article |
|---|---|
| Faculty \ School: | Faculty of Science > School of Biological Sciences |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Groups > Cancer Studies Faculty of Science > Research Groups > Cells and Tissues |
| Depositing User: | EPrints Services |
| Date Deposited: | 01 Oct 2010 13:38 |
| Last Modified: | 24 Sep 2024 09:52 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/1344 |
| DOI: | 10.1158/0008-5472.CAN-05-0470 |
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