Activated STAT3 Regulates Hypoxia-Induced Angiogenesis and Cell Migration in Human Glioblastoma
- Authors
- Kang, Shin-Hyuk; Yu, Mi Ok; Park, Kyung-Jae; Chi, Sung-Gil; Park, Dong-Hyuk; Chung, Yong-Gu
- Issue Date
- 11월-2010
- Publisher
- OXFORD UNIV PRESS INC
- Keywords
- Angiogenesis; Glioblastoma; Hypoxia; Migration; Signal transducer and activator of transcription 3
- Citation
- NEUROSURGERY, v.67, no.5, pp.1386 - 1395
- Indexed
- SCIE
SCOPUS
- Journal Title
- NEUROSURGERY
- Volume
- 67
- Number
- 5
- Start Page
- 1386
- End Page
- 1395
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/115371
- DOI
- 10.1227/NEU.0b013e3181f1c0cd
- ISSN
- 0148-396X
- Abstract
- BACKGROUND: Glioblastoma is the most common primary brain tumor, with typical histopathologic findings, pseudopalisading necrosis, and microvascular proliferation, all of which are associated with a poor prognosis. Hypoxia is known to affect these morphological features, but the underlying molecular mechanism has been poorly understood. OBJECTIVE: To determine the role of signal transducer and activator of transcription 3 (STAT3) in the malignant progression of glioblastoma under hypoxic conditions. METHODS: We studied STAT3 activation by hypoxic stress and its effect on hypoxia-induced angiogenesis and cell migration using U87, A172, T98, and U373 human glioblastoma cell lines. RESULTS: All four glioblastoma cells analyzed expressed detectable levels of STAT3 phosphorylation. Hypoxic stress markedly increased phosphorylated STAT3 level in a time-dependent fashion, and activated STAT3 was translocated into the nucleus. Hypoxic conditions led to a 30-50% increase in angiogenesis and cell migration, but these effects were significantly attenuated by small interfering ribonucleic acid-mediated knockdown of STAT3. Furthermore, STAT3 activation was associated with an elevated expression of hypoxic inducible factor-1, vascular endothelial growth factor, matrix metalloproteinase 2, and TWIST messenger ribonucleic acid and protein, which may play a critical role in hypoxia-induced angiogenesis and migration. CONCLUSION: STAT3 plays an important role in glioblastoma angiogenesis and migration triggered by hypoxia. Therefore, STAT3 might be a target for control of pseudopalisading necrosis and angiogenesis in glioblastoma.
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Collections - College of Medicine > Department of Medical Science > 1. Journal Articles
- Graduate School > Department of Life Sciences > 1. Journal Articles
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