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内皮素-1及内皮素受体在人脑膜瘤中的表达与定位。其在肿瘤生长中作用的证据。

Expression and localization of endothelin-1 and endothelin receptors in human meningiomas. Evidence for a role in tumoral growth.

作者信息

Pagotto U, Arzberger T, Hopfner U, Sauer J, Renner U, Newton C J, Lange M, Uhl E, Weindl A, Stalla G K

机构信息

Max-Planck Institute of Psychiatry, Clinical Institute, Munich, Germany.

出版信息

J Clin Invest. 1995 Oct;96(4):2017-25. doi: 10.1172/JCI118249.

DOI:10.1172/JCI118249
PMID:7560095
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC185840/
Abstract

In addition to its well-known homoeostatic actions in the cardiovascular system, ET-1 has been shown to constitute a potent growth regulatory peptide in various tissues. We have studied the expression of ET-1 and its receptors (ET-Ar and ET-Br) in human meningiomas (n = 35) as well as their involvement in cellular growth. By PCR of reverse-transcribed RNA we detected ET-1 mRNA in 91% (32 of 35), ET-Ar mRNA in 82% (29 of 35), and ET-Br mRNA in 42% (15 of 35) of human meningiomas examined. The localization of ET-1 mRNA, ET-Ar mRNA, and ET-1 peptide in tumoral cells was observed by in situ hybridization and immunohistochemistry, whereas ET-Br mRNA was expressed at low level only in cells belonging to blood vessels. In addition, we found that ET-1 stimulated [3H] thymidine incorporation in primary cell cultures of 20 meningiomas and that this effect could be blocked by BQ-123, a specific antagonist for ET-Ar. In contrast, RES-701-3, an antagonist of ET-Br, did not block the proliferative effect of ET-1. In conclusion, our data provide evidence that ET-1 constitutes an important growth factor for meningiomas acting via ET-Ar. We can hypothesize that ET-1, acting in concert with other growth factors and cytokines, is involved in the meningioma tumorigenesis.

摘要

除了在心血管系统中众所周知的稳态作用外，ET-1已被证明在各种组织中构成一种强大的生长调节肽。我们研究了ET-1及其受体（ET-Ar和ET-Br）在35例人脑膜瘤中的表达情况，以及它们在细胞生长中的作用。通过逆转录RNA的PCR检测，我们在所检测的人脑膜瘤中发现，91%（35例中的32例）存在ET-1 mRNA，82%（35例中的29例）存在ET-Ar mRNA，42%（35例中的15例）存在ET-Br mRNA。通过原位杂交和免疫组织化学观察了ET-1 mRNA、ET-Ar mRNA和ET-1肽在肿瘤细胞中的定位，而ET-Br mRNA仅在血管细胞中低水平表达。此外，我们发现ET-1刺激了20例脑膜瘤原代细胞培养物中[3H]胸苷的掺入，并且这种作用可被ET-Ar的特异性拮抗剂BQ-123阻断。相比之下，ET-Br的拮抗剂RES-701-3并未阻断ET-1的增殖作用。总之，我们的数据提供了证据，表明ET-1是通过ET-Ar发挥作用的脑膜瘤重要生长因子。我们可以推测，ET-1与其他生长因子和细胞因子协同作用，参与了脑膜瘤的肿瘤发生。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/397e/185840/00a73fc8b497/jcinvest00016-0334-c.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/397e/185840/6ce5dca59645/jcinvest00016-0334-d.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/397e/185840/b4eae09352e6/jcinvest00016-0334-e.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/397e/185840/a1501a557098/jcinvest00016-0334-f.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/397e/185840/ac3d08ecfe12/jcinvest00016-0335-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/397e/185840/750c58b15507/jcinvest00016-0336-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/397e/185840/9d97cc542736/jcinvest00016-0337-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/397e/185840/8d32208e72e9/jcinvest00016-0338-a.jpg
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Endothelins stimulate c-fos and nerve growth factor expression in astrocytes and astrocytoma.内皮素刺激星形胶质细胞和星形细胞瘤中c-fos和神经生长因子的表达。
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