Abstract LB-078: The role of CEACAM1 in neutrophil extracellular Trap mediated cancer metastasis
Notice bibliographique
Résumé
Abstract We have previously identified that Neutrophil Extracellular Traps (NETs) are an important contributing factor to the metastatic process. However, the underlying molecular mechanisms by which NETs facilitate metastasis remain unclear. Using mass spectrometry, amongst 583 distinct proteins, we identified CEACAM1 (CC1) in isolated human NETs and we sought to determine whether CC1 has a role in NET-mediated cancer metastasis. The presence of CC1 on NETs was confirmed by immunofluorescence. In vitro static adhesion of human colon cancer HT29 cells to isolated purified human NETs was reduced by 50% using a function blocking antibody against human CC1, but not isotype control, an effect equal to NET degradation with DNAse. Adhesion of murine colon cancer MC38-CC1L cells to C57BL/6 mouse neutrophils stimulated to produce NETs with phorbol myristate acetate (PMA) was increased 3-fold compared to untreated neutrophils, an effect that was completely attenuated with DNAse. PMA stimulation of neutrophils isolated from Ceacam1−/− knockout (KO) mice did not increase adhesion to MC38-CC1L cells. Using a parallel plate flow chamber, a physiologically relevant adhesion model under the shear conditions encountered in liver sinusoids, we flowed Lewis lung carcinoma (C10) cancer cells over neutrophils isolated from C57BL/6 or Ceacam1−/− KO mice. PMA-induced NET formation in C57BL/6 mouse neutrophils increased cancer cell adhesion 5-fold, an effect again completely attenuated by DNAse or use of neutrophils from Ceacam1−/− KO mice. Using a transwell chamber, MC38-CC1L cancer cells exposed to NET-stimulated Ceacam1−/− KO neutrophils had a 50% decrease in migration, compared to those exposed to NETs from C57BL/6 neutrophils. In order to delineate the role of CC1 in NET-related in vivo adhesion of cancer cells to liver sinusoids, we performed a series of neutrophil depletion and re-infusion experiments. C57BL/6 mice, depleted of neutrophils with anti-GR1 24 hrs prior, were re-infused with neutrophils isolated from C57BL/6 or Ceacam1−/− KO mice. This was followed by injection of MC38-CFSE labelled cells and hepatic intravital microscopy was used to quantify in vivo cancer cell adhesion and migration. PMA-stimulated C57BL/6 neutrophils prior to re-infusion was associated with a two-fold increase in adhesion compared to PMA-stimulated Ceacam1−/− KO neutrophils, an effect that was completely attenuated using DNAse. Our data support the notion that CEACAM1 is, at least in part, responsible for the increased cancer cell migration mediated by Neutrophil Extracellular Traps. We have thereby identified NET-associated CEACAM1 as a putative therapeutic target to prevent the metastatic progression of cancer cells. Citation Format: Phil Vourtzoumis, Rashmi Seth, Roni Rayes, Sara Najmeh, Jonathan Cools-Lartigue, Betty Giannias, France Bourdeau, Nicole Beauchemin, Simon Rousseau, Richard Blumberg, Jonathan D. Spicer, Lorrenzo Edwin Ferri. The role of CEACAM1 in neutrophil extracellular Trap mediated cancer metastasis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-078.
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 ».