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Functional expression of TWEAK and the receptor Fn14 in human malignant ovarian tumors: possible implication for
1Department of Gynecology and Obstetrics, Renji Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, PR China.
Abstract:
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.
Insights
Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor-inducible 14 (Fn14) are expressed in malignant ovarian tumors, suggesting a potential tumor suppressor role by activating macrophages and serving as a diagnostic marker.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- The expression and role of TWEAK/Fn14 in ovarian cancer are not fully understood.
- Ovarian cancer remains a significant health challenge with a need for novel diagnostic markers and therapeutic targets.
Purpose of the Study:
- To investigate the expression of TWEAK and Fn14 in human ovarian tumors.
- To elucidate the role of TWEAK in ovarian cancer progression in vitro.
- To explore the potential of TWEAK/Fn14 as a diagnostic marker for malignant ovarian tumors.
Main Methods:
- Immunohistochemistry (IHC) was used to detect TWEAK and Fn14 expression in human ovarian tumor tissues.
- In vitro cell culture models (HO-8910PM cells and THP-1 macrophages) were employed to study TWEAK's effects on proliferation, invasion, and cytokine production.
- Conditioned media from activated macrophages were used to assess their impact on ovarian cancer cells.
Main Results:
- TWEAK and Fn14 were significantly expressed in malignant ovarian tumors but absent in normal or benign tissues.
- TWEAK alone or TNF-α alone did not inhibit HO-8910PM cell proliferation; combined TWEAK and TNF-α showed an inhibitory effect.
- TWEAK activated macrophages to produce TNF-α and MCP-1, and conditioned media from these activated macrophages inhibited ovarian cancer cell proliferation and invasion.
Conclusions:
- TWEAK/Fn14 signaling, through macrophage activation, may act as an ovarian tumor suppressor mechanism.
- The specific expression of TWEAK/Fn14 in malignant ovarian tumors suggests its potential utility as a diagnostic biomarker.
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