Cancers (Jun 2022)

Epithelial-to-Mesenchymal Transition Drives Invasiveness of Breast Cancer Brain Metastases

  • Andreia S. Margarido,
  • Rebeca Uceda-Castro,
  • Kerstin Hahn,
  • Roebi de Bruijn,
  • Lennart Kester,
  • Ingrid Hofland,
  • Jeroen Lohuis,
  • Danielle Seinstra,
  • Annegien Broeks,
  • Jos Jonkers,
  • Marike L. D. Broekman,
  • Pieter Wesseling,
  • Claire Vennin,
  • Miguel Vizoso,
  • Jacco van Rheenen

DOI
https://doi.org/10.3390/cancers14133115
Journal volume & issue
Vol. 14, no. 13
p. 3115

Abstract

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(1) Background: an increasing number of breast cancer patients develop lethal brain metastases (BM). The complete removal of these tumors by surgery becomes complicated when cells infiltrate into the brain parenchyma. However, little is known about the nature of these invading cells in breast cancer brain metastasis (BCBM). (2) Methods: we use intravital microscopy through a cranial window to study the behavior of invading cells in a mouse model of BCBM. (3) Results: we demonstrate that BCBM cells that escape from the metastatic mass and infiltrate into brain parenchyma undergo epithelial-to-mesenchymal transition (EMT). Moreover, cells undergoing EMT revert to an epithelial state when growing tumor masses in the brain. Lastly, through multiplex immunohistochemistry, we confirm the presence of these infiltrative cells in EMT in patient samples. (4) Conclusions: together, our data identify the critical role of EMT in the invasive behavior of BCBM, which warrants further consideration to target those cells when treating BCBM.

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