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

• Authors: Atreyi Dasqupta, Cleveland Clinic; Baisakhi Raychaudhuri, Cleveland Clinic; Talat Haqqi, Cleveland Clinic; Richard Prayson, Cleveland Clinic; Erwin Van Meir, Emory University; Michael Vogelbaum, Cleveland Clinic; Saikh Jaharul Haque, Cleveland Clinic
• Journal Title: EJC Supplements
• Volume: Volume 45, Number 4
• Publisher: Elsevier | 2009-01-05, Pages 677-684
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1016/j.ejca.2008.11.027
• Subjects: Biology, Neuroscience; Health Sciences, Oncology
• 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

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.