Skip to main content
Log in

Effect of endothelin-1 as growth factor on a human glioma cell line; its characteristic promotion of DNA synthesis

  • Laboratory Investigation
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

In addition to its powerful vasoconstrictive activity, endothelin-1 (ET-1) has been recognized to stimulate DNA synthesis in some cell lines. In this study, we confirmed the existence of ET-1 receptor in YKG-1 human glioma cells, and investigated its effect on DNA synthesis in YKG-1 for 6 consecutive days, comparing it with that of epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and insulin-like growth factor-I (IGF-I).

Scatchard analysis of the binding data revealed the presence of a single class of high-affinity binding molecule. The apparent dissociation constant (Kd) was 5.2 × 10−9 M and the maximal binding capacity (B max) was 4.7 × 104 sites/cell. The percentage of non-cycling cells was initially more than 85%, and decreased to 55.40%, 24.22%, 11.50%, and 7.51% on days 1, 2, 4, and 6, respectively, after ET-1 stimulation. Although ET-1 reduces the fraction of non-cycling cells more slowly than other growth factors such as EGF, PDGF and IGF-I, it reaches the same level as the others by day 6.

These results indicate that YKG-1 human glioma cells have ET-1 receptors and that ET-1 initiates a peculiar slow induction of DNA synthesis in these cells, suggesting that secondary factors might exist to accelerate the DNA synthesis in response to ET-1.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y, Yazaki Y, Goto K, Masaki T: A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 332: 411–415, 1988

    Google Scholar 

  2. Kobayashi H, Hayashi M, Kobayashi S, Kabuto M, Handa Y, Kawano H, Ide H: Cerebral vasospasm and vasoconstriction caused by endothelin. Neurosurgery 28: 673–678, 1991

    Google Scholar 

  3. Suzuki R, Masaoka H, Hirata Y, Marumo F, Isotani E, Hirakawa K: The role of endothelin-1 in the origin of cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage. J Neurosurg 77: 96–100, 1992

    Google Scholar 

  4. Inoue A, Yanagisawa M, Kimura S, Kasuya Y, Miyauchi T, Goto K, Masaki T: The human endothelin family: three structurally and pharmacologically distinct isopeptides predicted by three separate genes. Proc Natl Acad Sci USA 86: 2863–2867, 1989

    Google Scholar 

  5. Kusuhara M, Yamaguchi K, Ohnishi A, Abe K, Kimura S, Oono H, Hori S, Nakamura Y: Endothelin potentiates growth factor-stimulated DNA synthesis in Swiss 3T3 cells. Jpn J Cancer Res 80: 302–305, 1989

    Google Scholar 

  6. Takuwa N, Takuwa Y, Yanagisawa M, Yamashita K, Masaki T: A novel vasoactive peptide endothelin stimulates mitogenesis through inositol lipid turnover in Swiss 3T3 fibroblasts. J Biol Chem 264: 7856–7861, 1989

    Google Scholar 

  7. Shichiri M, Hirata Y, Nakajima T, Ando K, Imai T, Yanagisawa M, Masaki T, Marumo F: Endothelin-1 is an autocrine/paracrine growth factor for human cancer cell lines. J Clin Invest 87: 1867–1871, 1991

    Google Scholar 

  8. Vigne P, Marsault R, Breittmayer JP, Freiin C: Endothelin stimulates phosphatidylinositol hydrolysis and DNA synthesis in brain capillary endothelial cells. Biochem J 266: 415–420, 1990

    Google Scholar 

  9. MacCumber MW, Ross CA, Snyder SH: Endothelin in brain: receptors, mitogenesis, and biosynthesis in glial cells. Proc Natl Acad Sci USA 87: 2359–2363, 1990

    Google Scholar 

  10. Zhang W, Sakai N, Fu T, Okano Y, Hirayama H, Takenaka K, Yamada H, Nozawa Y: Diacylglycerol formation and DNA synthesis in endothelin-stimulated rat C6 glioma cells: the possible role of phosphatidylcholine breakdown. Neurosci Lett 123: 164–166, 1991

    Google Scholar 

  11. Kanno H, Kuwabara T, Shinonaga M, Chang CC, Tanaka Y, Sugio Y, Morita H, Yasumitsu H, Umeda M, Nagashima Y: Establishment of a human glioma cell line bearing a homogeneously staining chromosomal region and releasing alpha- and beta-type transforming growth factors. Acta Neuropathol (Berl) 79: 30–36, 1989

    Google Scholar 

  12. Urayama O, Nakao M, Nagamune H, Sugiyama H: Coupling of membrane-bound and detergent-solubilized sodium- and potassium-activated ATPase to p-benzoquinone-treated microtiter plates. Anal Biochem 141: 194–198, 1984

    Google Scholar 

  13. Hoshi H, McKeehan WL: Brain- and liver cell-derived factors are required for growth of human endothelial cells in serum-free culture. Proc Natl Acad Sci USA 81: 6413–6417, 1984

    Google Scholar 

  14. Dolbeare F, Gratzner H, Pallavicini MG, Gray JW: Flow cytometric measurement of total DNA content and incorporated bromodeoxyuridine. Proc Natl Acad Sci USA 80: 5573–5577, 1983

    Google Scholar 

  15. Bobik A, Grooms A, Millar JA, Mitchell A, Grinpukel S: Growth factor activity of endothelin on vascular smooth muscle. Am J Physiol 258: 408–415, 1990

    Google Scholar 

  16. Nakaki T, Nakayama M, Yamamoto S, Kato R: Endothelin-mediated stimulation of DNA synthesis in vascular smooth muscle cells. Biochem Biophys Res Commun 158: 880–883, 1989

    Google Scholar 

  17. Kurihara M, Ochi A, Kawaguchi T, Niwa M, Kataoka Y, Mori K: Localization and characterization of endothelin receptors in human gliomas: a growth factor? Neurosurgery 27: 275–281, 1990

    Google Scholar 

  18. Jaffer FE, Knauss TC, Poptic E, Abboud HE: Endothelin stimulates PDGF secretion in cultured human mesangial cells. Kidney Int 38: 1193–1198, 1990

    Google Scholar 

  19. Jones CR, Hiley CR, Pelton JT, Mohr M: Autoradiographic visualization of the binding sites for (125I)endothelin in rat and human brain. Neurosci Lett 97: 276–279, 1989

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Asano, T., Aoyagi, M., Hirakawa, K. et al. Effect of endothelin-1 as growth factor on a human glioma cell line; its characteristic promotion of DNA synthesis. J Neuro-Oncol 18, 1–7 (1994). https://doi.org/10.1007/BF01324597

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01324597

Key words

Navigation