Abstract LB-297: The EMT inhibitor AB-16B5 interacts with specific isoforms of secreted clusterin
Notice bibliographique
Résumé
Abstract Secreted clusterin (sCLU) exhibits elevated expression in several cancer indications. sCLU plays a pro-survival role in tumors and, more recently, it was found to be a potent stimulator of the epithelial-to-mesenchymal transition (EMT). These findings led to the development of a monoclonal antibody, AB-16B5, that interacts with a specific EMT-inducing domain in sCLU resulting in abrogation of migration and invasion of many types of cancer cells. We previously showed that blocking tumor-associated sCLU with AB-16B5 reduced the expression of mesenchymal markers and restored the expression of epithelial markers in human tumor xenografts, observations that were in line with inhibition of EMT in vivo. Consequently, this resulted in reduced metastatic invasion and increased response to cytotoxic agents in animal models of human cancer. We now report new results that shed light on the biochemical differences between sCLU that is secreted by tumor cells or normal cells. Using two-dimensional gel electrophoresis, we found that there was a difference in the number and composition of sCLU isoforms present in the plasma of cancer patients compared with those expressed in healthy individuals. In particular, the post-translational modifications were more complex on sCLU secreted from tumor cells compared with those present in sCLU from healthy individuals. Moreover, AB-16B5 was found to specifically interact with several of the isoforms expressed from tumor cells but exhibited a reduced ability to interact with sCLU from plasma from healthy individuals. We also examined the interaction between AB-16B5 and tumor-associated sCLU in vivo. In these studies, injection of AB-16B5 conjugated to a fluorophore in mice harboring sub-cutaneously implanted human pancreatic tumor xenografts resulted in a rapid enrichment of fluorescence signal in the tumors. Interestingly, administration of high concentrations of human recombinant sCLU immediately prior to injection of the AB-16B5 fluorophore-conjugate still resulted in enrichment of fluorescence signal in the tumors, albeit at slightly lower intensity than was observed in the absence of recombinant sCLU. Our findings indicate that AB-16B5 can efficiently interact with tumor-associated sCLU despite the presence of excess concentrations of sCLU in the circulation. Taken together, our results suggest that AB-16B5 has increased affinity for sCLU isoforms that are specifically expressed from tumor cells that have undergone an EMT. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-297. doi:1538-7445.AM2012-LB-297
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
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 | 0,001 | 0,000 |
| 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) | 0,002 | 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 ».