Localization of the endothelin system in human diffuse astrocytomas

• Published in: Cancer 2005-09, Vol.104 (5), p.1049-1057
• Main Authors: Naidoo, Vinogran, Naidoo, Strinivasen, Mahabeer, Rajeshree, Raidoo, Deshandra M.
• Format: Article
• Language: English
• Subjects: Adult; Aspartic Acid Endopeptidases - analysis; Astrocytoma - chemistry; Astrocytoma - etiology; Biological and medical sciences; Endothelin-1 - analysis; Endothelin-1 - genetics; Endothelin-1 - physiology; Endothelin-Converting Enzymes; Female; Humans; immunocytochemistry; Immunohistochemistry; in situ RT‐PCR; Male; Medical sciences; Medicin och hälsovetenskap; Metalloendopeptidases - analysis; Neurology; Receptor, Endothelin A - analysis; Receptor, Endothelin B - analysis; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; tumor astrocytes; Tumors; Tumors of the nervous system. Phacomatoses; vasoconstriction
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.21277

BACKGROUND 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). METHODS 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. RESULTS 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. CONCLUSIONS 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. Human astrocytomas (WHO Grade II) express components of the endothelin system. The role of these components in mitogenesis, antiapoptosis, and vasoregulation implicate this system in tumorigenesis.