Proteolytic and Opportunistic Breaching of the Basement Membrane Zone by Immune Cells during Tumor Initiation

Maaike Van Den Berg, Lucy MacCarthy-Morrogh, Deborah Carter, Josie Morris, Isabel Ribeiro Bravo, Yi Feng*, Paul Martin

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)

5 Citations (Scopus)
149 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)2837-2846.e4
Number of pages15
JournalCell Reports
Volume27
Issue number10
Early online date4 Jun 2019
DOIs
Publication statusPublished - 4 Jun 2019

Keywords

  • cancer
  • inflammation
  • zebrafish
  • CLEM
  • basement membrane zone
  • neutrophils
  • macrophages
  • cell motility
  • collagen

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    Van Den Berg, M., MacCarthy-Morrogh, L., Carter, D., Morris, J., Ribeiro Bravo, I., Feng, Y., & Martin, P. (2019). Proteolytic and Opportunistic Breaching of the Basement Membrane Zone by Immune Cells during Tumor Initiation. Cell Reports, 27(10), 2837-2846.e4. https://doi.org/10.1016/j.celrep.2019.05.029