en
Scientific article
Open access
English

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

Published inCancer Discovery, vol. 6, no. 6, p. 630-649
Publication date2016
Abstract

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.

Keywords
  • 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
Affiliation Not a UNIGE publication
Citation (ISO format)
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
Main files (1)
Article (Accepted version)
accessLevelPublic
Identifiers
ISSN of the journal2159-8274
102views
51downloads

Technical informations

Creation07/08/2021 5:35:00 PM
First validation07/08/2021 5:35:00 PM
Update time03/16/2023 1:06:28 AM
Status update03/16/2023 1:06:27 AM
Last indexation01/17/2024 1:58:53 PM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack