title: Cell surface overexpression of alphavbeta5 integrin impedes alphavbeta3-mediated migration of the human ovarian adenocarcinoma cell line IGROV1.
abstract: Human ovarian surface epithelium and epithelial tumors express integrin alphavbeta5, which can interact with vitronectin. In addition, in vitro acquisition of cisplatin resistance by alphavbeta3-expressing IGROV1 cells is accompanied by cell-surface expression of integrin alphavbeta5. To further explore the role of alphavbeta5 in ovarian carcinoma cells, IGROV1 cells were stably transfected with a human beta5 integrin cDNA construct, and three beta5 transfectant clones were selected for the expression of alphavbeta5 integrin at their cell surface. Despite a delayed entry in the exponential phase of growth, beta5-transfectant cells kept a proliferation ability similar to that of parental cells, while their growth rate was hindered in the presence of an anti-alphavbeta5 blocking antibody. Only simultaneous blockade of alphavbeta3 and alphavbeta5 by specific antibodies impeded the adhesion to vitronectin of beta5 transfectants and of the beta5-expressing cisplatin-resistant variant IGROV1-R10, suggesting that the two heterodimers cooperated in the regulation of this process. Cell surface expression of alphavbeta5 resulted in an attenuation of alphavbeta3-mediated migration on vitronectin. Alphavbeta5 participated to migration events in the absence of exogenous growth factors only in one transfectant clone and in IGROV1-R10 cells. Finally, the response to cisplatin was not significantly modified in beta5 transfectants when compared to IGROV1 parental cells.
authors.affiliation: GRECAN, Université de Caen-Basse Normandie and Centre de Lutte contre le Cancer François Baclesse, Avenue du Général Harris, 14076 Caen Cedex 05, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Maubant
authors.forename: Johanne
authors.initials: J
authors.lastname: Leroy-Dudal
authors.forename: Franck
authors.initials: F
authors.lastname: Carreiras
authors.forename: Edwige
authors.initials: E
authors.lastname: Deslandes
authors.forename: Françoise
authors.initials: F
authors.lastname: Duigou
authors.forename: Cathy
authors.initials: C
authors.lastname: Staedel
authors.forename: Pascal
authors.initials: P
authors.lastname: Gauduchon
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D019138:Antibodies, Blocking / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000473:pathology*; D019030:Receptors, Vitronectin / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured; D019096:Vitronectin / Q000378:metabolism
chemical_list: D019138:Antibodies, Blocking; D039302:Integrin alphaVbeta3; D016023:Integrins; D019030:Receptors, Vitronectin; D019096:Vitronectin; C064660:integrin alphaVbeta5; D002945:Cisplatin