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Localization of the endothelin system in human diffuse astrocytomas
Author(s) -
Naidoo Vinogran,
Naidoo Strinivasen,
Mahabeer Rajeshree,
Raidoo Deshandra M.
Publication year - 2005
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.21277
Subject(s) - endothelin receptor , receptor , endothelin 1 , messenger rna , microbiology and biotechnology , immunocytochemistry , endothelins , biology , in situ hybridization , pathology , endocrinology , medicine , gene , biochemistry
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 ET A and ET B 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, ET A and ET B 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, ET A and ET B 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 ET A and ET B 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 ET B receptors, may promote tumorigenesis. Cancer 2005. © 2005 American Cancer Society.