A Lamb1Dendra2 mouse model identifies basement-membrane-producing origins and dynamics in PyMT breast tumors

Jessica Morgner*, Laura Bornes, Kerstin Hahn, Carmen Lopez-Iglesias, Lona Kroese, Colin E. J. Pritchard, Claire Vennin, Peter J. Peters, Ivo Huijbers, Jacco van Rheenen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The basement membrane (BM) around tumor lobes forms a barrier to prevent cancer cells from invading the surrounding tissue. Although myoepithelial cells are key producers of the healthy mammary epithelium BM, they are nearly absent in mammary tumors. To study the origin and dynamics of the BM, we developed and imaged a laminin beta1-Dendra2 mouse model. We show that the turnover of laminin beta1 is faster in the BMs that surround the tumor lobes than in the BMs that surround the healthy epithelium. Moreover, we find that epithelial cancer cells and tumor-infiltrating endothelial cells synthesize laminin beta1 and that this production is temporarily and locally heterogeneous, leading to local discontinuity of the BM laminin beta1. Collectively, our data draw a new paradigm for tumor BM turnover in which the disassembly happens at a constant rate, and a local misbalance of compensating production leads to reduction or even complete disappearance of the BM.
Original languageEnglish
Pages (from-to)535-549.e5
Number of pages21
JournalDevelopmental Cell
Volume58
Issue number7
DOIs
Publication statusPublished - 10 Apr 2023

Keywords

  • MYOEPITHELIAL CELLS
  • LAMININ ISOFORMS
  • MAMMARY-GLAND
  • EXPRESSION
  • ADHESION

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