Abstract A39: A newly defined role of clusterin in the formation of exosomes derived from prostate cancer cells
Notice bibliographique
Résumé
Abstract Introduction: Molecular chaperones, including heat-shock proteins (Hsps), help cells cope with stress-induced protein misfolding and aggregation and play prominent roles in cellular signaling and transcriptional regulatory networks asscociated with cancer progression and treatment resistance. Clusterin (CLU) is a stress-activated cytoprotective chaperone, up-regulated in Castration Resistant Prostate Cancer (CPRC), that confers hormone and chemo-resistance. Targeting inhibition of CLU using OGX-011 enhances treatment-induced cell death therapeutic response as is currently in clinical trials of men with advanced prostate cancer. Recent studies have linked cancer with exosome formation; exosomes are 30–100 nm membrane-bound compartments secreted from normal and tumor cells. The mechanisms underlying exosome formation and secretion are not fully understood. Factors such as stage of cancer, cell type and cell cycle could affect the amount and composition of exosomes formed and secreted. Since CLU has chaperone activity with a potent ability to inhibit amorphous and fibrillar aggregation of many different proteins, we hypothesize that it can influence exosome formation and release from androgen independent PCa cells. Methods-Results: PC3 cells were seeded and grown in DMEM with 5% FBS until 70% confluency. Media was changed to 5% charcoal strip serum DMEM and finally to a serum free media for 72 hours before exosome isolation. Exosomes were purified from the conditioned media using differential centrifugation after remove cell debris and protein aggregates. Further analysis by transmission electron microscopy detected the integrity of purified exosomes and their concentration. Western blot analysis was also used to probe for different exosome markers including Actin, Tubulin, TSG 101, HSP70 and CD36. In this study, we functionally analyzed the role of Clusterin in relation to exosome formation from PC-3 PCa cells. Clusterin was knocked down in PC3 cells using siRNA, and confirmed with western blot analysis. The content of Clusterin in exosomes after knockdown remains unchanged while, in contrast, cells become Clusterin depleted. Upon Clusterin knockdown in PC3 cells we also observe a dramatic reduction in the amount of exosomes formed. Conclusion: We have found high levels of CLU in exosomes derived from PCa cells. Our data suggests that CLU may serve a role in exosome formation since knocking it down by siRNA dramatically inhibits the quantity of exosomes formed. Citation Information: Clin Cancer Res 2010;16(7 Suppl):A39
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,002 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».