Cell surface overexpression of alphavbeta5 integrin impedes alphavbeta3-mediated migration of the human ovarian adenocarcinoma cell line IGROV1.
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.
Maubant
Sylvie
S
GRECAN, Université de Caen-Basse Normandie and Centre de Lutte contre le Cancer François Baclesse, Avenue du Général Harris, 14076 Caen Cedex 05, France.
Leroy-Dudal
Johanne
J
Carreiras
Franck
F
Deslandes
Edwige
E
Duigou
Françoise
F
Staedel
Cathy
C
Gauduchon
Pascal
P
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
D019138:Antibodies, Blocking; D039302:Integrin alphaVbeta3; D016023:Integrins; D019030:Receptors, Vitronectin; D019096:Vitronectin; C064660:integrin alphaVbeta5; D002945:Cisplatin