title: Functional expression of TWEAK and the receptor Fn14 in human malignant ovarian tumors: possible implication for ovarian tumor intervention.
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.
authors.affiliation: Department of Gynecology and Obstetrics, Renji Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, PR China.
authors.forename: Liying
authors.initials: L
authors.lastname: Gu
authors.forename: Lan
authors.initials: L
authors.lastname: Dai
authors.forename: Cong
authors.initials: C
authors.lastname: Cao
authors.forename: Jing
authors.initials: J
authors.lastname: Zhu
authors.forename: Chuanwei
authors.initials: C
authors.lastname: Ding
authors.forename: Hai-Bo
authors.initials: HB
authors.lastname: Xu
authors.forename: Lihua
authors.initials: L
authors.lastname: Qiu
authors.forename: Wen
authors.initials: W
authors.lastname: Di
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018932:Chemokine CCL2 / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D018920:Coculture Techniques; D000074049:Cytokine TWEAK; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D000074050:TWEAK Receptor; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000494:pharmacology; D048069:Tumor Necrosis Factors / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D014408:Biomarkers, Tumor; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D000074049:Cytokine TWEAK; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; C000613297:TNFRSF12A protein, human; C109743:TNFSF12 protein, human; D000074050:TWEAK Receptor; D014409:Tumor Necrosis Factor-alpha; D048069:Tumor Necrosis Factors