PloS one, 2013-03, Vol.8 (3), p.e57436
2013
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- Autor(en) / Beteiligte
- Titel
- Functional expression of TWEAK and the receptor Fn14 in human malignant ovarian tumors: possible implication for ovarian tumor intervention
- Ist Teil von
- PloS one, 2013-03, Vol.8 (3), p.e57436
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2013
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- The aim of this current study was to investigate the expression of the tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor-inducible 14 (Fn14) in human malignant ovarian tumors, and test TWEAK's potential role on tumor progression in cell models in-vitro. Using immunohistochemistry (IHC), we found that TWEAK and its receptor Fn14 were expressed in human malignant ovarian tumors, but not in normal ovarian tissues or in borderline/benign epithelial ovarian tumors. High levels of TWEAK expression was detected in the majority of malignant tumors (36 out of 41, 87.80%). Similarly, 35 out of 41 (85.37%) malignant ovarian tumors were Fn14 positive. In these malignant ovarian tumors, however, TWEAK/Fn14 expression was not corrected with patients' clinical subtype/stages or pathological features. In vitro, we demonstrated that TWEAK only inhibited ovarian cancer HO-8910PM cell proliferation in combination with tumor necrosis factor-α (TNF-α), whereas either TWEAK or TNF-α alone didn't affect HO-8910PM cell growth. TWEAK promoted TNF-α production in cultured THP-1 macrophages. Meanwhile, conditioned media from TWEAK-activated macrophages inhibited cultured HO-8910PM cell proliferation and invasion. Further, TWEAK increased monocyte chemoattractant protein-1 (MCP-1) production in cultured HO-8910PM cells to possibly recruit macrophages. Our results suggest that TWEAK/Fn14, by activating macrophages, could be ovarian tumor suppressors. The unique expression of TWEAK/Fn14 in malignant tumors indicates that it might be detected as a malignant ovarian tumor marker.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0057436Titel-ID: cdi_plos_journals_1346587372
- Format
- –
- Schlagworte
- Apoptosis, Biomarkers, Tumor - genetics, Biomarkers, Tumor - metabolism, Carcinoma - genetics, Carcinoma - metabolism, Carcinoma - pathology, Care and treatment, Cell culture, Cell Line, Tumor, Cell Movement - drug effects, Cell proliferation, Cell Proliferation - drug effects, Cell receptors, Chemokine CCL2 - agonists, Chemokine CCL2 - genetics, Chemokine CCL2 - metabolism, Coculture Techniques, Conditioning, Cytokine TWEAK, Development and progression, Female, Fibroblast growth factor, Fibroblast growth factors, Gene expression, Gene Expression Regulation, Neoplastic - drug effects, Genetic aspects, Health aspects, Humans, Immunohistochemistry, Inhibition, Kinases, Laboratories, Macrophage Activation - drug effects, Macrophages, Macrophages - cytology, Macrophages - drug effects, Macrophages - metabolism, Medicine, Monocyte chemoattractant protein, Monocyte chemoattractant protein 1, Ovarian cancer, Ovarian carcinoma, Ovarian Neoplasms - genetics, Ovarian Neoplasms - metabolism, Ovarian Neoplasms - pathology, Receptors, Tumor Necrosis Factor - genetics, Receptors, Tumor Necrosis Factor - metabolism, Recombinant Proteins - genetics, Recombinant Proteins - metabolism, Recombinant Proteins - pharmacology, Signal Transduction - drug effects, Suppressors, Tissues, Tumor markers, Tumor Necrosis Factor-alpha - biosynthesis, Tumor Necrosis Factor-alpha - pharmacology, Tumor necrosis factor-TNF, Tumor necrosis factor-α, Tumor Necrosis Factors - genetics, Tumor Necrosis Factors - metabolism, Tumor Necrosis Factors - pharmacology, Tumors, TWEAK protein, TWEAK Receptor