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

Abstract

(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.

Re-purposing the pro-senescence properties of doxorubicin to introduce immunotherapy in breast cancer brain metastasis

“…In order to identify new approaches to render BCBM sensitive to immunotherapy, we used a mouse BCBM model generated via serial intracranial transplantations and carotid injections in immunocompetent Friend Virus B (FVB/NRj) inbred mice of tumor pieces derived from MMTV-PyMT mice that carry an E-cadherin-mCFP transgene 36 (see STAR Methods and Figure 1 A and Margarido et al. 37 ). Following six rounds of enrichment in the brain, we generated organoids from the BCBM and we engineered them with H2B-Dendra2 and luciferase constructs for imaging purposes (from herein referred to as “PyMT BCBM organoids”).…”

Origin, Metastasis, Harm, Recognition and Capture, and Elimination of Circulating Tumor Cells

“…The occurrence of the invasive process requires changes in cell morphology and phenotype as well as changes in the surrounding environment. [ 99 ] During invasion, three important processes will be located in dynamic regulatory networks, including adhesion, ECM reorganization, and motility. [ 100 ] Normal epithelial cells are usually polarized along the apical‐basal end axis, forming structures such as tight junctions and adherens junctions.…”

The Journey of Cancer Cells to the Brain: Challenges and Opportunities

“…Cancer cells preparing to invade the surrounding tissue as their first step of the metastatic journey undergo epithelial–mesenchymal transition (EMT) [ 10 , 11 ]. This complex process constitutes cells shedding their epithelial phenotype to become less differentiated, more aggressive, and more stem-cell-like [ 12 ].…”