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Cilengitide targets pediatric glioma and neuroblastoma cells through cell detachment and anoikis induction.

Abstract：

:The prognosis of children with high-grade glioma or high-risk neuroblastoma remains poor. Cilengitide is a selective antagonist of αvβ3 and αvβ5 integrins, which are involved in tumor growth and development of metastasis. We have evaluated the effects of cilengitide on pediatric glioma and neuroblastoma cell lines for the first time. Expression levels of αvβ3 and αvβ5 were determined by flow cytometry in three neuroblastoma and five pediatric glioma cell lines compared with adult U87-MG before and after irradiation. Cell detachment, cytotoxicity, and cell growth under nonadhesive conditions were measured using the MTS assay. Cell death and apoptosis were assessed by annexin-V/propidium iodide staining. The varying αvβ3 and αvβ5 expression levels were unrelated to tumor grade. Irrespective of the αvβ5 expression level, the pediatric cells expressing αvβ3 were dose dependently sensitive to cilengitide. UW479 cells expressed only αvβ5 integrin and were not sensitive to cilengitide, suggesting that cilengitide's action largely depends on αvβ3 inhibition. Cell detachment resulted in a higher cytotoxicity in pediatric glioma compared with U87-MG cells, which seem able to grow despite the significant cilengitide-induced cell detachment. Growth kinetics on polyHEMA showed that only pediatric glioma cells were sensitive to anoikis and so died after cilengitide-induced detachment. Furthermore, irradiation of glioma cells increased αvβ3 expression slightly but not cilengitide sensitivity. Cilengitide's action on glioma and neuroblastoma cells appears to be dependent on αvβ3 expression and sensitivity to anoikis. Cilengitide is able to target pediatric glioma and neuroblastoma cells in vitro directly and efficiently. Tumor context could validate these promising observations.

journal_name

Anticancer Drugs

journal_title

Anti-cancer drugs

authors

Leblond P,Dewitte A,Le Tinier F,Bal-Mahieu C,Baroncini M,Sarrazin T,Lartigau E,Lansiaux A,Meignan S

doi

10.1097/CAD.0b013e328362edc5

subject

Has Abstract

pub_date

2013-09-01 00:00:00

pages

818-25

issue

eissn

0959-4973

issn

1473-5741

journal_volume

pub_type

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Cilengitide targets pediatric glioma and neuroblastoma cells through cell detachment and anoikis induction.