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

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Samenvatting

(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 pa-renchyma 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 sam-ples. (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.

Originele taal-2Engels
Artikelnummer3115
TijdschriftCancers
Volume14
Nummer van het tijdschrift13
DOI's
StatusGepubliceerd - 25 jun. 2022

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