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Cited by 230Cytokine Signaling Pathways and InteractionsAngiogenesis and VEGF in CancerPleural and Pulmonary Diseases

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Autocrine IL-6-induced Stat3 activation contributes to the pathogenesis of lung adenocarcinoma and malignant pleural effusion

Yeh, H-H, Lai, W-W, Chen, H H W, Liu, H-S, Su, W-C·2006·Oncogene
DOI 10.1038/sj.onc.1209464
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Abstract

Malignant pleural effusion (MPE) is a poor prognostic sign for patients with non-small-cell lung cancer (NSCLC). The generation of MPE is largely regulated by vascular endothelial growth factor (VEGF), and upregulation of VEGF by Stat3 has been observed in several types of tumor cells. In this study, we demonstrate constitutively activated Stat3 in several human lung cancer cell lines and in tumor cells infiltrated in the pleurae of patients with adenocarcinoma cell lung cancer (ADCLC) and MPE. The observations suggest that activated Stat3 plays a role in the pathogenesis of ADCLC. In PC14PE6/AS2 cells, a Stat3-positive human ADCLC cell line, autocrine IL-6 activated Stat3 via JAKs, not via Src kinase. PC14PE6/AS2 cells express higher VEGF mRNA and protein than do Stat3-negative PC14PE6/AS2/dnStat3 cells. In an animal model, PC14P6/AS2/dnStat3 cells produced no MPE and less lung metastasis than did PC14P6/AS2 cells. PC14PE6/AS2 cells also expressed higher VEGF protein, microvessel density, and vascular permeability in tumors than did PC14P6/AS2/dnStat3 cells. Therefore, we hypothesize that autocrine IL-6 activation of Stat3 in ADCLC may be involved in the formation of malignant pleural effusion by upregulating VEGF. Higher levels of IL-6 and VEGF were also found in the pleural fluids of patients with ADCLC than in patients with congestive heart failure. The autocrine IL-6/Stat3/VEGF signaling pathway may also be activated in patients with ADCLC and MPE. These findings provide novel targets for the management of MPE.

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Metadata

Authors
Yeh, H.-H., Lai, W.-W., Chen, H. H. W., Liu, H.-S., & Su, W.-C.
Affiliations
  • National Cheng Kung University (TW)
  • National Cheng Kung University Hospital (TW)
Corresponding author
  • Liu, H-S
  • Su, W-C
ORCID
Su, W-C
Venue
Oncogene
Publisher
Springer Science and Business Media LLC
Published
2006-03-06
Volume
25
Issue
31
Pages
4300-4309
ISSN
  • 0950-9232 (ISSN-L)
  • 1476-5594
DOI
10.1038/sj.onc.1209464
OpenAlex
W2022200777
Cited by
230
References
0
Citations by year
2026: 4 · 2025: 5 · 2024: 6 · 2023: 13 · 2022: 14 · 2021: 13 · 2020: 11 · 2019: 15 · 2018: 8 · 2017: 11 · 2016: 9 · 2015: 16 · 2014: 6 · 2013: 16 · 2012: 17
FWCI
6.26
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Oncogene (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Pleural and Pulmonary Diseases
Keywords
malignant pleural effusion, lung adenocarcinoma, interleukin-6, STAT3 activation, autocrine signaling, vascular endothelial growth factor, JAK signaling, non-small cell lung cancer, lung metastasis, tumor angiogenesis, pleural fluid biomarkers, microvessel density, vascular permeability
MeSH terms
Adenocarcinoma, Animals, Female, Humans, Lung Neoplasms, Male, Mice, Inbred BALB C, Mice, Nude, Interleukin-6, Pleural Effusion, Malignant, Vascular Endothelial Growth Factor A, Cell Line, Tumor, STAT3 Transcription Factor, Mice

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