Altered adhesion properties and alphav integrin expression in a cisplatin-resistant human ovarian carcinoma cell line.
In order to elucidate the mechanisms underlying the development of chemoresistance in ovarian cancer, we have previously established the IGROV1-R10 cisplatin-resistant cell line by mimicking a clinical protocol of drug administration on IGROV1 human ovarian carcinoma cells. Both IGROV1 and IGROV1-R10 cells were able to grow as a monolayer and to release cell clusters into the medium. However, IGROV1-R10 cells exhibited an enhanced capacity to detach from the monolayer as compared to the parental cells. When substrate adhesion was prevented, IGROV1-R10 cells were able to survive and to proliferate as cell clusters, even at a low cell density, whereas IGROV1 cells massively died. To explore the underlying mechanisms, we have been interested in alphav integrins, which have been implicated in some aspects of ovarian cancer biology. Both IGROV1 and IGROV1-R10 adherent cells expressed alphavbeta3 integrin. During cell growth, alphavbeta5 integrin accumulated at the surface of a majority of IGROV1-R10 cells from the monolayer, whereas only a faint expression of this integrin was observed in a minority of IGROV1 cells. The growth of IGROV1-R10 cells, but not of IGROV1 cells, was partly inhibited by a specific alphavbeta5-blocking antibody suggesting that alphavbeta5 integrin contributed to IGROV1-R10 cell proliferation.
Maubant
Sylvie
S
Groupe Régional d'Etudes sur le Cancer, Université de Caen, Laboratoire de Cancérologie Expérimentale, Centre François Baclesse, Route de Lion-sur-mer, 14076 Caen Cedex 05, France.
Cruet-Hennequart
Séverine
S
Poulain
Laurent
L
Carreiras
Franck
F
Sichel
François
F
Luis
José
J
Staedel
Cathy
C
Gauduchon
Pascal
P
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002448:Cell Adhesion; D002455:Cell Division / Q000502:physiology; D002945:Cisplatin / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000032:analysis; D019008:Drug Resistance, Neoplasm; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D019030:Receptors, Vitronectin / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D016023:Integrins; D019030:Receptors, Vitronectin; C064660:integrin alphaVbeta5; D001973:Bromodeoxyuridine; D002945:Cisplatin