title: Wnt5A exerts immunomodulatory activity in the human ovarian cancer cell line SKOV-3.
abstract: The purpose of this study was three fold: (1) to reveal the implications of Wnt5A for cytokine and chemokine production by human ovarian cancer cell line SKOV-3 cells, (2) to determine the influence of Wnt5A on chemotactic SKOV-3 cell migration, and (3) to assess the effect of inflammatory mediators on Wnt5A expression levels and to describe its underlying molecular mechanisms. A cytokine array was performed using a conditioned medium harvested from SKOV-3 cells transfected with specific siRNAs against Wnt5A or with scrambled siRNA and a transfection reagent alone as negative controls for 48 h. Chemotactic cell migration was performed using transwells. Inflammation-induced Wnt5A expression was determined by treating cells with recombinant human (rh) IL-1β, IFNβ, or TNFα alone or in combination with STAT3 and NF-κB inhibitors for different time durations. The cytokine array showed the suppression of GCSF, GM-CSF, IL-1α, IL-2, IL-13, and MCP-3 production, whereas cell RANTES and IL-7 showed increased levels in Wnt5A knock-down cells compared with those in controls. Chemotactic migration decreased significantly when the conditioned medium from Wnt5A knock-down cells was applied to the upper chamber of the transwell. Compared with the control, there were 30-fold and five-fold increases in Wnt5A mRNA levels in cells treated, with rhIL-1β and rhIFNβ, respectively after 8 h (P < 0.001). Compared with the control, TNF-α had a 1.8-fold increased levels of Wnt5A mRNA after 4 h (P < 0.01). Both NF-κB and STAT3 inhibitors decreased inflammation-induced Wnt5A expression. This study revealed a previously unrecognized immunomodulatory role of endogenous Wnt5A in ovarian cancer cells, which could further influence chemotactic cell migration.
authors.affiliation: Department of Animal Physiology, Developmental Biology Laboratory, School of Biology, College of Science, University of Tehran, Tehran, Iran.
authors.forename: Somayeh
authors.initials: S
authors.lastname: Arabzadeh
authors.affiliation: Department of Animal Physiology, Developmental Biology Laboratory, School of Biology, College of Science, University of Tehran, Tehran, Iran.
authors.forename: Ghamartaj
authors.initials: G
authors.lastname: Hossein
authors.affiliation: Nanobiotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran.|Immunology Research Center, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Amir Hassan
authors.initials: AH
authors.lastname: Zarnani
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D002633:Chemotaxis / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D005260:Female; D006801:Humans; D016899:Interferon-beta / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D016328:NF-kappa B / Q000276:immunology; D010051:Ovarian Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D051153:Wnt Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D000071818:Wnt-5a Protein
chemical_list: D018925:Chemokines; D016207:Cytokines; D053583:Interleukin-1beta; D007376:Interleukin-2; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D016899:Interferon-beta
keywords: Wnt5A; chemokines; cytokines; inflammation; migration; ovarian cancer