title: Differential Wnt11 expression related to Wnt5a in high- and low-grade serous ovarian cancer: implications for migration, adhesion and survival.
abstract: Wnt is a powerful signaling pathway that plays a crucial role in cell fate determination, survival, proliferation and motility during development, in adult tissues and cancer. The aims of the present study were three fold: i) to assess Wnt11 immunoexpression and its possible relationship with Wnt5a in high- and low-grade human serous ovarian cancer (HGSC and LGSC) specimens; ii) to assess Wnt11 expression levels in Wnt5a overexpressing SKOV-3 cells; iii) to reveal the role of Wnt11 in viability, adhesion, migration and invasion of SKOV-3 cells using recombinant human Wnt11 (rhWnt11). Immunohistochemistry revealed a significant difference in Wnt11 expression between HGSC and LGSC groups (p=0.001). Moreover, a positive correlation was observed between Wnt5a and Wnt11 expression in the HGSC (r=0.713, p=0.001), but not the LGSC group. The expression of Wnt11 was decreased by 35% in Wnt5a overexpressing cells (SKOV-3/Wnt5a) compared to mock controls. Similarly Wnt11 expression levels were decreased by 47% in the presence of exogenous Wnt5a compared to untreated cells. In the presence of rhWnt11, 31% increased cell viability (p<0.001) and 21% increased cell adhesion to matrigel (p<0.01) were observed compared to control. Cell migration was increased by 1.6-fold with rhWnt11 as revealed by transwell migration assay (p<0.001). However, 45% decreased cell invasion was observed in the presence of rhWnt11 compared to control (p<0.01). Our results may suggest that differential Wnt11 immunoexpression in HGSC compared to LGSC could play important roles in serous ovarian cancer progression and may be modulated by Wnt5a expression levels.
authors.affiliation: Department of Animal Physiology, Developmental Biology Laboratory, School of Biology, University College of Science, University of Tehran, Tehran, Iran E-mail : ghossein@khayam.ut.ac.ir.
authors.forename: Farnaz
authors.initials: F
authors.lastname: Jannesari-Ladani
authors.forename: Ghamartaj
authors.initials: G
authors.lastname: Hossein
authors.forename: Narges
authors.initials: N
authors.lastname: Izadi-Mood
mesh_terms: D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D018284:Cystadenocarcinoma, Serous / Q000473:pathology*; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000473:pathology*; D010957:Plasmids / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D014162:Transfection; D051153:Wnt Proteins / Q000096:biosynthesis* / Q000235:genetics; D060449:Wnt Signaling Pathway; D000071818:Wnt-5a Protein
chemical_list: D011518:Proto-Oncogene Proteins; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C540523:Wnt11 protein, human