Stat3 activation is required for the growth of U87 cell-derived tumours in mice.
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 2mm 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.
Dasgupta
Atreyi
A
Department of Cancer Biology, NB-40, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Raychaudhuri
Baisakhi
B
Haqqi
Talat
T
Prayson
Richard
R
Van Meir
Erwin G
EG
Vogelbaum
Michael
M
Haque
Saikh Jaharul
SJ
D000818:Animals; D017209:Apoptosis; D015687:Cell Hypoxia; D049109:Cell Proliferation; D004195:Disease Models, Animal; D018450:Disease Progression; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D005822:Genetic Vectors; D005909:Glioblastoma / Q000098:blood supply / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D016867:Immunocompromised Host; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D016019:Survival Analysis; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D009363:Neoplasm Proteins; D050796:STAT3 Transcription Factor