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- W2599046052 abstract "2079 Background: Integrins regulate cellular adhesion and transmit signals important for cell survival, proliferation, differentiation and motility. Both αvβ3 and αvβ5 integrins are upregulated in glioma cells, and therefore, integrin inhibition may represent a promising therapeutic strategy in glioblastoma. Methods: SMA-560 and GL-261 mouse glioma cells were cultured as adherent monolayers in serum-containing medium or as sphere cultures in neurobasal medium. Integrin function was inhibited using RNA interference, blocking antibodies or pharmacological inhibitors. Cell death after integrin inhibition was examined by flow cytometry. Immunoblot was used to assess apoptosis and autophagy. Results: GL-261 and SMA-560 glioma cells grown under standard conditions uniformly detached and formed large cell clusters after integrin gene silencing or pharmacological inhibition using EMD-121974 (cilengitide), a synthetic Arg-Gly-Asp-motif peptide, or GLPG0187, a non-peptidic integrin inhibitor. After 120 h, the clusters induced by integrin inhibition disintegrated and cells died. In contrast, no morphological effects were observed when cell lines were grown as stem-like sphere cultures. Since Poly-HEMA-mediated detachment had similar effects on cell viability as integrin inhibition, we postulated that cell death may result from detachment alone which was confirmed using various permissive and non-permissive substrates. No signs of apoptosis or autophagy were found using Annexin V/PI staining, DEVD-amc cleaving assay or caspase-3 and LC3A/B immunoblot. Recently, we demonstrated that integrin inhibition results in an inhibition of the TGF-β pathway in human glioma cells. Addition of recombinant TGF-β2 indeed partially rescued integrin inhibition-induced cell death, whereas exposure to the TGF-β receptor inhibitor SD-208 increased the number of dead cells. Conclusions: Cell death following integrin inhibition is essentially necrotic and may involve the TGF-β pathway." @default.
- W2599046052 created "2017-04-07" @default.
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- W2599046052 date "2013-05-20" @default.
- W2599046052 modified "2023-09-27" @default.
- W2599046052 title "Induction of atypical anoikis in glioma cells through inhibition of integrin functions." @default.
- W2599046052 doi "https://doi.org/10.1200/jco.2013.31.15_suppl.2079" @default.
- W2599046052 hasPublicationYear "2013" @default.
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