Maubant Sylvie, Cruet-Hennequart Séverine, Poulain Laurent, Carreiras Franck, Sichel François, Luis José, Staedel Cathy, Gauduchon Pascal
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.
Int J Cancer. 2002 Jan 10;97(2):186-94. doi: 10.1002/ijc.1600.
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.
为了阐明卵巢癌化疗耐药发生的潜在机制,我们之前通过模拟对IGROV1人卵巢癌细胞的临床给药方案,建立了IGROV1-R10顺铂耐药细胞系。IGROV1和IGROV1-R10细胞都能够单层生长并向培养基中释放细胞簇。然而,与亲代细胞相比,IGROV1-R10细胞从单层脱离的能力增强。当阻止底物黏附时,即使在低细胞密度下,IGROV1-R10细胞也能够作为细胞簇存活和增殖,而IGROV1细胞则大量死亡。为了探究潜在机制,我们对αv整合素产生了兴趣,其在卵巢癌生物学的某些方面发挥作用。IGROV1和IGROV1-R10贴壁细胞均表达αvβ3整合素。在细胞生长过程中,αvβ5整合素在单层的大多数IGROV1-R10细胞表面积累,而在少数IGROV1细胞中仅观察到这种整合素的微弱表达。一种特异性αvβ5阻断抗体部分抑制了IGROV1-R10细胞的生长,但未抑制IGROV1细胞的生长,这表明αvβ5整合素促进了IGROV1-R10细胞的增殖。