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Author Notes:

Corresponding author: Address: Department of Cancer Biology, NB-40, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA. Tel.: +1 (216) 445 6622; fax: +1 (216) 445 6269. haquej@ccf.org (S. J. Haque)

We thank Drs. Janet Houghton, Gene Barnett, Serpil Erzurum, Pankaj Sharma, Fred Hsieh and Robert Weil for critical comments, Phyllis Harbor and Saroja N. Devi for technical assistance and Dr. Judith Drazba and Rikhia Chakraborty for assistance in imaging.

Conflict of interest statement: None declared.

Subjects:

Research Funding:

This work was supported by Grants R01CA095006 and R01CA116804 from the National Institutes of Health to SJH and EGVM, respectively.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Oncology
  • ONCOLOGY
  • Apoptosis
  • Angiogenesis
  • Glioblastoma multiforme
  • Hypoxia
  • Stat3
  • VEGF
  • GLIOBLASTOMA-MULTIFORME CELLS
  • ANGIOGENIC SWITCH
  • MALIGNANT GLIOMA
  • VEGF EXPRESSION
  • HYPOXIA
  • INTERLEUKIN-4
  • DORMANCY
  • NECROSIS
  • BIOLOGY

Stat3 activation is required for the growth of U87 cell-derived tumours in mice

Tools:

Journal Title:

EJC Supplements

Volume:

Volume 45, Number 4

Publisher:

, Pages 677-684

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Previously we reported that Stat3 is persistently activated in GBM tumours and derived cell lines. Hypoxia, necrosis and neo-angiogenesis are hallmarks of GBM. To unfold the contribution of activated Stat3 to the growth of GBM, we generated human GBM cell line (U87)-derived stable clones expressing a dominant negative mutant (DN)-Stat3 in a hypoxia-inducible manner, and examined their tumour-forming potentials in immune-compromised mice. We found that the parental and vector control cell-derived tumours grew steadily, whereas DN-Stat3-expressing clone-derived tumours failed to grow beyond 2 mm of thickness in mouse flanks. This blockade of tumour growth was associated with induction of tumour cell apoptosis and suppression of tumour angiogenesis. Consistent with this, mice bearing orthotopically implanted DN-Stat3-expressing clones survived significantly longer than the control mice. These data suggest that activated Stat3 is required for the growth of GBM, and that targeting Stat3 may intervene with the growth of GBM. © 2008 Elsevier Ltd. All rights reserved.

Copyright information:

© 2008 Elsevier Ltd. Published by Elsevier Inc. All rights reserved.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported License (http://creativecommons.org/licenses/by-nc-nd/3.0/).

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