Cancer Cell Biology
Matrix-degrading proteases ADAMTS4 and ADAMTS5 (disintegrins and metalloproteinases with thrombospondin motifs 4 and 5) are expressed in human glioblastomas
Article first published online: 7 JUL 2005
Copyright © 2005 Wiley-Liss, Inc.
International Journal of Cancer
Volume 118, Issue 1, pages 55–61, 1 January 2006
How to Cite
Held-Feindt, J., Paredes, E. B., Blömer, U., Seidenbecher, C., Stark, A. M., Mehdorn, H. M. and Mentlein, R. (2006), Matrix-degrading proteases ADAMTS4 and ADAMTS5 (disintegrins and metalloproteinases with thrombospondin motifs 4 and 5) are expressed in human glioblastomas. Int. J. Cancer, 118: 55–61. doi: 10.1002/ijc.21258
- Issue published online: 26 OCT 2005
- Article first published online: 7 JUL 2005
- Manuscript Accepted: 8 APR 2005
- Manuscript Received: 17 AUG 2004
- Deutsche Forschungsgemeinschaft (DFG). Grant Number: HE 3400/1-1
- extracellular matrix;
Brain tumors, in particular glioblastomas, have a high morbidity and mortality, mainly due to their invasive nature. A prerequisite for this invasiveness is cell migration based on increased expression of proteases digesting the extracellular matrix. Brevican, an important extracellular proteoglycan that is upregulated in glioblastomas, can be degraded by certain proteases. We demonstrate that in human glioblastomas secretory proteases like ADAMTS4 and ADAMTS5 (aggrecanases 1 and 2; ADAMTS = a disintegrin and metalloproteinase with thrombospondin motifs) are expressed on the mRNA and protein levels in considerable amounts. Real-time RT-PCR shows a higher levels of ADAMTS4 and 5 expressions in glioblastomas in situ, compared to cultured human glioblastoma cells. The upregulation of these proteases in vivo by cytokines may explain this difference. In vitro, transforming growth factor-β induces ADAMTS4, but less ADAMTS5, and interleukin-1β ADAMTS5, but not ADAMTS4. As demonstrated by immunohistochemistry and confocal microscopy in situ, ADAMTS5 expression is confined to proliferating glioblastoma cells of surgical tumor sections and with lower intensity to astroglial cells in normal brain sections, as opposed to brevican. In vitro, glioblastoma-derived ADAMTS5 degrades recombinant human brevican to several smaller fragments. Our results show that ADAMTS4 and 5 are upregulated on proliferating glioblastoma cells and these proteases may contribute to their invasive potential. © 2005 Wiley-Liss, Inc.