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Localization of the endothelin system in human diffuse astrocytomas
Article first published online: 8 JUL 2005
Copyright © 2005 American Cancer Society
Volume 104, Issue 5, pages 1049–1057, 1 September 2005
How to Cite
Naidoo, V., Naidoo, S., Mahabeer, R. and Raidoo, D. M. (2005), Localization of the endothelin system in human diffuse astrocytomas. Cancer, 104: 1049–1057. doi: 10.1002/cncr.21277
- Issue published online: 17 AUG 2005
- Article first published online: 8 JUL 2005
- Manuscript Accepted: 4 APR 2005
- Manuscript Revised: 15 MAR 2005
- Manuscript Received: 13 SEP 2004
- tumor astrocytes;
- in situ RT-PCR
Endothelin-1 (ET-1), a vasoconstrictor and mitogen, has recently been implicated in the pathogenesis of human glioblastoma, neuroblastoma, and meningioma. ET-1, formed by proteolysis of the propeptide big ET-1 by endothelin-converting enzyme-1 (ECE-1), mediates its cellular actions through ETA and ETB receptors. Because only immunoreactive ET-1 has been observed within human astrocytic tumor cells, the authors investigated the localization of the entire ET-1 system (ET-1 mRNA, ET-1, ECE-1, ETA and ETB receptors) in surgical samples of human diffuse astrocytomas WHO Grade II (n = 6).
ET-1 mRNA expression was elucidated by in situ reverse transcriptase polymerase chain reaction (RT-PCR) using synthetic primers. Polyclonal antibodies were used to localize ET-1, ECE-1, ETA and ETB receptors by immunocytochemistry.
All ET components were detected in the six tumor samples. Intense (3+) cytoplasmic ET-1 mRNA labeling was observed in more than 75% of cells in all 6 astrocytomas. Up to 75% of tumor cells displayed intense ET-1 and ECE-1 immunolabeling distributed throughout their cytoplasm. Immunoreactive ETA and ETB receptors, observed in 25% to 75% of astrocytic tumor cells, were of moderate intensity. In addition, all components of the ET system were seen within endothelial cells of tumor blood vessels.
The presence of ET-1 mRNA, ECE-1, and ET-1 within tumor astrocytes suggests local ET synthesis and processing. The mitogenic and antiapoptotic properties of ET-1, as well as the vasodilatory signaling of ETB receptors, may promote tumorigenesis. Cancer 2005. © 2005 American Cancer Society.