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Neutrophils suppress intraluminal NK cell-mediated tumor cell clearance and enhance extravasation of disseminated carcinoma cells

Publié dansCancer Discovery, vol. 6, no. 6, p. 630-649
Date de publication2016
Résumé

Immune cells promote the initial metastatic dissemination of carcinoma cells from primary tumors. In contrast to their well-studied functions in the initial stages of metastasis, the specific roles of immunocytes in facilitating progression through the critical later steps of the invasion-metastasis cascade remain poorly understood. Here, we define novel functions of neutrophils in promoting intraluminal survival and extravasation at sites of metastatic dissemination. We show that CD11b(+)/Ly6G(+) neutrophils enhance metastasis formation via two distinct mechanisms. First, neutrophils inhibit natural killer cell function, which leads to a significant increase in the intraluminal survival time of tumor cells. Thereafter, neutrophils operate to facilitate extravasation of tumor cells through the secretion of IL1β and matrix metalloproteinases. These results identify neutrophils as key regulators of intraluminal survival and extravasation through their cross-talk with host cells and disseminating carcinoma cells.

Mots-clés
  • Adoptive Transfer
  • Animals
  • Biomarkers
  • Carcinoma/genetics/immunology/metabolism/pathology
  • Cell Communication
  • Cell Line
  • Tumor
  • Cell Movement
  • Cell Survival
  • Cytokines/biosynthesis
  • Disease Models
  • Animal
  • Endothelial Cells/metabolism
  • Heterografts
  • Humans
  • Immunity
  • Innate
  • Immunophenotyping
  • Killer Cells
  • Natural/immunology/metabolism
  • Matrix Metalloproteinases/metabolism
  • Mice
  • Mice
  • Knockout
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neutrophils/immunology/metabolism
  • Phenotype
Structure d'affiliation Pas une publication de l'UNIGE
Citation (format ISO)
SPIEGEL, Asaf et al. Neutrophils suppress intraluminal NK cell-mediated tumor cell clearance and enhance extravasation of disseminated carcinoma cells. In: Cancer Discovery, 2016, vol. 6, n° 6, p. 630–649. doi: 10.1158/2159-8290.CD-15-1157
Fichiers principaux (1)
Article (Accepted version)
accessLevelPublic
Identifiants
ISSN du journal2159-8274
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Informations techniques

Création08.07.2021 17:35:00
Première validation08.07.2021 17:35:00
Heure de mise à jour16.03.2023 01:06:28
Changement de statut16.03.2023 01:06:27
Dernière indexation17.01.2024 13:58:53
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