Experimental Cancer

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Transforming growth factor-β-mediated autocrine growth regulation of gliomas as detected with phosphorothioate antisense oligonucleotides

  1. Piotr Jachimczak1,
  2. Birgit Hessdörfer1,
  3. Klaus Fabel-Schulte1,
  4. Cäcilie Wismeth1,
  5. Wolfgang Brysch2,
  6. Karl-Hermann Schlingensiepen3,
  7. Albrecht Bauer1,
  8. Armin Blesch1,
  9. Ulrich Bogdahn1,*

Article first published online: 6 DEC 1998

DOI: 10.1002/(SICI)1097-0215(19960126)65:3<332::AID-IJC10>3.0.CO;2-C

Issue

International Journal of Cancer

International Journal of Cancer

Volume 65, Issue 3, pages 332–337, 26 January 1996

Additional Information

How to Cite

Jachimczak, P., Hessdörfer, B., Fabel-Schulte, K., Wismeth, C., Brysch, W., Schlingensiepen, K.-H., Bauer, A., Blesch, A. and Bogdahn, U. (1996), Transforming growth factor-β-mediated autocrine growth regulation of gliomas as detected with phosphorothioate antisense oligonucleotides. International Journal of Cancer, 65: 332–337. doi: 10.1002/(SICI)1097-0215(19960126)65:3<332::AID-IJC10>3.0.CO;2-C

Author Information

  1. 1

    Department of Neurology, University of Würzburg, 97080 Würzburg, Germany

  2. 2

    Biognostik Ltd., 37079 Göttingen, Germany

  3. 3

    Max-Planck-Institute for Biophysical Chemistry, 37077 Göttingen, Germany

*Department of Neurology, University of Würzburg Josef-Schneider-Str. 11, 97080 Würzburg, Germany. Fax: 0049 931 201 2697

Publication History

  1. Issue published online: 6 DEC 1998
  2. Article first published online: 6 DEC 1998
  3. Manuscript Revised: 12 OCT 1995
  4. Manuscript Received: 13 APR 1995

Funded by

  • Deutsche Keebshiffe. Grant Number: W-73/91/Bo-2

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Abstract

Transforming growth factors-β1 and -β2 (TGF-β1 and -β2) are important growth-regulatory proteins for astroglial neoplasms. We analyzed their role in tumor-cell proliferation in 12 glioma cell lines, employing phosphorothioate antisense oligodeoxynucleotides (S-ODNs, 14 mer), specifically targeted against the coding sequences of TGF-β1-mRNA and TGF-β2-mRNA. TGF-β1-S-ODNs inhibited cell proliferation in 5 of 12 gliomas, whereas TGF-β2-S-ODNs reduced the cell proliferation in all glioma cell lines, compared to nonsense-S-ODN-treated and S-ODN-untreated cells as controls. The efficacy and specificity of antisense effects was validated by Northern-blot analysis and determination of protein concentrations in culture supernatants (ELISA). Exogenous hrTGF-β1 either stimulated or inhibited the cell lines, whereas pnTGF-β2 stimulated the proliferation of most glioma cells. Blocking the extracellular pathway of TGF-β by neutralizing antibodies only slightly inhibited those cell lines, which were markedly stimulated by TGF-βs. As the effects of TGF-β2-S-ODNs were much stronger than those of TGF-β neutralizing antibodies, we postulate that the endogenously produced TGF-β2 control glioma-cell proliferation, in part by an intracellular loop. © 1996 Wiley-Liss, Inc.

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