Abstract 2972: Neutrophil extracellular traps sequester circulating tumor cells <i>in vitro</i> and in a murine model of metastasis
Notice bibliographique
Résumé
Abstract Introduction: Emerging evidence suggests that neutrophil mediated factors may be implicated in cancer progression, however the mechanisms for this are unclear. Neutrophil extracellular traps (NET's) constitute a mechanism by which pathogens are trapped and killed in extracellular neutrophil derived DNA webs containing antimicrobial proteins. The role of NETs in cancer progression is unknown. We hypothesized that circulating tumor cells could become trapped within NET's, potentially favoring the development of metastatic disease. Materials and Methods: Static adhesion assays were performed using H59 lung cancer cells added to neutrophil monolayers. NETs were induced with phorbol myristate acetate (PMA). NET formation was inhibited with DNAse. Adhesion under dynamic conditions was quantified under flow at 1 dyne/cm2. Lung cancer cells (A549 or H59) were perfused over neutrophil monolayers stimulated with PMA, PMA + DNAse, or media alone, and tumor cell adhesion was quantified. NET formation after stimulation was verified by staining extracellular DNA with Sytox green and assessed for the presence of tumor cell-NET association. To study in vivo interactions between NETs and cancer cells, control and bacterial lipopolysaccharide (LPS) stimulated mice (4 hours prior) were prepared for spinning disc confocal intravital microscopy and H59 cells were injected intra-arterially. Neutrophils were identified by injection of anti-GR1 Alexa 647 conjugated mAb and NETs were stained by injection of anti-histone H2A.X Alexa 555 conjugated mAb.Results: Static H59 cells adhesion to neutrophils stimulated with PMA increased 8-fold over media alone, an effect that was completely attenuated by DNAse. Under flow conditions, PMA increased A549 and H59 cell adherence to neutrophil monolayers 10-fold over media alone, DNAse reduced cancer cell adhesion in PMA stimulated neutrophils by a factor of 3. Staining with Sytox green demonstrated a high degree of co-localization of NETs with clusters of malignant cells in neutrophils stimulated with PMA alone, but not in the presence of DNAse or media alone. Mice stimulated with LPS demonstrated heavy histone H2A.X staining suggestive of NET formation and co-localization with H59 cells. LPS induced NET formation correlated with a previously published 50% increase in H59 cell adhesion to hepatic sinusois. Conclusions: Neutrophil extracellular trap formation is associated with increased adherence and capture of cancer cells in both static and dynamic conditions. This is the first time this in vitro finding has been described and correlates with the first demonstration of in vivo NET/cancer cell interactions. These results suggest a novel mechanism by which neutrophils may promote cancer progression. 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 2972. doi:1538-7445.AM2012-2972
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) | 0,001 | 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 | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,006 | 0,002 |
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 ».