ZFIN ID: ZDB-PUB-190606-7
Proteolytic and Opportunistic Breaching of the Basement Membrane Zone by Immune Cells during Tumor Initiation
van den Berg, M.C.W., MacCarthy-Morrogh, L., Carter, D., Morris, J., Ribeiro Bravo, I., Feng, Y., Martin, P.
Date: 2019
Source: Cell Reports   27: 2837-2846.e4 (Journal)
Registered Authors: Feng, Yi, Martin, Paul
Keywords: CLEM, basement membrane zone, cancer, cell motility, collagen, inflammation, macrophages, neutrophils, zebrafish
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Basement Membrane/cytology
  • Basement Membrane/enzymology*
  • Basement Membrane/metabolism
  • Basement Membrane/ultrastructure
  • Carcinogenesis/genetics
  • Carcinogenesis/immunology*
  • Carcinogenesis/ultrastructure
  • Cell Proliferation
  • Collagen/metabolism
  • Disease Models, Animal
  • Epidermis/growth & development
  • Epidermis/immunology
  • Epidermis/pathology
  • Extracellular Matrix/enzymology
  • Extracellular Matrix/metabolism*
  • Goblet Cells/cytology*
  • Goblet Cells/metabolism
  • Goblet Cells/ultrastructure
  • Macrophages/cytology*
  • Macrophages/enzymology
  • Macrophages/immunology
  • Macrophages/ultrastructure
  • Metalloendopeptidases/antagonists & inhibitors
  • Metalloendopeptidases/metabolism
  • Microscopy, Electron, Transmission
  • Neutrophils/cytology*
  • Neutrophils/enzymology
  • Neutrophils/immunology
  • Neutrophils/ultrastructure
  • Proteolysis/drug effects
  • Skin Neoplasms/enzymology
  • Skin Neoplasms/immunology*
  • Skin Neoplasms/metabolism
  • Skin Neoplasms/ultrastructure
  • Zebrafish
PubMed: 31167131 Full text @ Cell Rep.
FIGURES
ABSTRACT
Cancer-related inflammation impacts significantly on cancer development and progression. From early stages, neutrophils and macrophages are drawn to pre-neoplastic cells in the epidermis, but before directly interacting, they must first breach the underlying extracellular matrix barrier layer that includes the basement membrane. Using several different skin cancer models and a collagen I-GFP transgenic zebrafish line, we have undertaken correlative light and electron microscopy (CLEM) to capture the moments when immune cells traverse the basement membrane. We show evidence both for active proteolytic burrowing and for the opportunistic use of pre-existing weak spots in the matrix layer. We show that these small holes, as well as much larger, cancer cell-generated or wound-triggered gaps in the matrix barrier, provide portals for immune cells to access cancer cells in the epidermis and thus are rate limiting in cancer progression.
ADDITIONAL INFORMATION