Abstract 1091: Procoagulant receptor tissue factor provokes the escape from brain tumor dormancy.
Notice bibliographique
Résumé
Abstract Occult persistence of transformed cells is known to precede the onset of clinically apparent malignancies, accompany disease remission and micrometastasis. While the mechanisms governing this dormant state remain poorly understood, tissue injury and wound healing responses have often been implicated in its cessation, but the surrounding circumstances remain largely obscure. Notably, the activation of hemostasis represents the first response to the exogenous and endogenous tissue injury, and is linked to inflammation, angiogenesis and growth promoting microenvironment. Tissue factor (TF) acts as the main trigger of the coagulation cascade in this setting, and is known to be overexpressed in cancer cells, including in high grade brain tumors such as glioblastoma (GBM). Here we report that in a model of GBM, the TF-mediated activation of the coagulation system may act as the sufficient initial trigger in the cessation of tumor dormancy, and the onset of inflammation and angiogenesis. We also document that while TF may play a role in the subsequent tumor progression, its expression by cancer and host cells may no longer be absolutely required in established tumors. Thus, we observed that indolent human glioma cells (U373) remain viable, but dormant for over 250 days post subcutaneous and orthotopic inoculation, with no evidence of tumor growth, as detected by bioluminescent monitoring. The enforced expression of TF is sufficient to trigger tumor formation by these cells, albeit after long latency (30-90 days). During this latent phase TF-expressing glioma cells, but not their TF-negative counterparts, are able to recruit rich stroma, containing CD11b+ myeloid cells and CD105+ blood vessels. These cells also evolve to become rapidly tumorigenic and gain a dramatic change to their transcriptome. Similar aggressiveness can also be induced in U373 cells by the expression of the oncogenic epidermal growth factor receptor variant (EGFRvIII), which also provokes upregulation of TF and onset of the procoagulant phenotype (U373vIII cells). Targeting TF in U373vIII tumors, as well as their implantation into TF-hypomorphic recipients (low-TF mice) delays, but does not abrogate experimental GBM progression. We generated spontaneous GBM tumors by intracranial injection of the oncogenic cDNA (SV40, N-ras), which becomes expressed in brain astrocytes under the control of the Sleeping Beauty (SB) transposase. Disruption of the TF gene in the astrocytic lineage of such mice (Cre/nestinTF-/-) resulted in a partial tumor growth inhibition. We postulate that activation of the coagulation system (via TF) may play a role in disruption of the dormant behavior of brain tumor cells and can serve as targets in prevention of disease onset. However, targeting TF alone is only partially effective as a measure to control the growth of established astrocytic tumors. Acknowledgments: We thank Dr. John Ohlfest for providing us with the SB transposon system. Citation Format: Nathalie Magnus, Delphine Garnier, Brian Meehan, Maryam Hashemi, Tae-Hoon Lee, Chloe Milsom, Nada Jabado, Rafal Pawlinski, Nigel Mackman, Janusz Rak. Procoagulant receptor tissue factor provokes the escape from brain tumor dormancy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1091. doi:10.1158/1538-7445.AM2013-1091
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 machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 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 | 0,000 |
| 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 | 0,001 |
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 source (Gemma direct ou Codex distillé), 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 ».