Abstract LB-258: Neutrophil extracellular traps sequester circulating tumor cells via beta 1 integrin mediated interactions
Notice bibliographique
Résumé
Abstract Introduction: Post-operative infectious complications in cancer patients confer an increased risk of death from distant metastasis, and activated neutrophils appear to be central cellular players in this phenomenon. We have previously demonstrated that Neutrophil extracellular traps (NETs), composed of extracellular neutrophil-derived DNA webs, are intricately implicated in this process by directly binding and capturing circulating tumor cells. However, the mechanisms mediating this interaction remain completely unexplored. We hypothesized that tumor cells adhere to NETs specifically through interactions between neoplastic and neutrophil-derived β 1 integrins. Methods: In vitro, NETs isolated from phorbol myristate acetate (PMA) activated neutrophils from healthy volunteers were plated on cover slips and human lung or colorectal cancer (A549 or HT29) adhesion assessed. In some experiments, cancer cell adhesion was assessed in the presence of DNAse, RGD peptide, or anti- β 1 integrin antibody (4B4). In vivo, cecal ligation and puncture (CLP) was used to induce NET formation and A549 cells (siRNA anti- β 1 integrin transfected or control) were injected via the intrasplenic route to assess real time single cell migration by hepatic intravital microscopy. Results: Adhesion of cancer cells to NET isolates was decreased 2-3 fold in the presence of DNAse and proteinase K, indicating the possibility of protein-protein interactions. Pretreatment of malignant cells with RGD peptide, known to inhibit integrin mediated adhesion, similarly resulted in a 2-3 fold decrease in tumor cell adhesion compared to isolated NETs alone. Adhesion of A549 and HT29 cells to NET isolates after pretreatment with function blocking anti- β 1 integrin antibody was 1/3 that of untreated cells. Following PMA stimulation, β 1 integrin staining co-localized within extracellular DNA but was absent in unstimulated neutrophils. Adhesion in vivo was reduced 2 fold after siRNA knockdown of β 1 integrin in A549 cells 24 hours following CLP compared to untreated cells. Hepatic intravital microscopy after CLP demonstrates widespread NET deposition demonstrated by DNA and histone H2A.X deposition. NETs were found to stain positive for β 1 integrin. Beta 1 integrin staining was increased after CLP compared to sham, and was abrogated by neutrophil depletion. Conclusions: This study is the first to implicate β 1 integrin mediated interactions as a mechanism for tumor-NET adhesion. Cell surface expression of β 1 integrins on tumor cells was necessary for tumor cell adhesion to NETs both in vitro and in vivo. Analysis of NETs both in vitro and in vivo demonstrated β 1 integrin expression, implicating integrin hetero-dimerization as a possible adhesive mechanism. Citation Format: Sara Najmeh, Jonathan Cools-Lartigue, Stephen Gowing, Jonahan Spicer, Braedon McDonald, Betty Giannias, France Bourdeau, Paul Kubes, Lorenzo Edwin Ferri. Neutrophil extracellular traps sequester circulating tumor cells via beta 1 integrin mediated interactions. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-258. doi:10.1158/1538-7445.AM2014-LB-258
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 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,004 | 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 ».