Issue 14, 2024

Impact of brain organoid-derived sEVs on metastatic adaptation and invasion of breast carcinoma cells through a microphysiological system

Abstract

Brain metastases are common in triple-negative breast cancer (TNBC), suggesting a complex process of cancer spread. The mechanisms enabling TNBC cell adaptation and proliferation in the brain remain unclear. Small extracellular vesicles (sEVs) play a crucial role in communication between breast carcinoma cells and the brain. However, the lack of relevant models hinders understanding of sEV-mediated communication. The present study assesses the impact of brain organoid-derived sEVs (BO-sEVs) on various behaviours of the MDA-MB-231 cell line, chosen as a representative of TNBC in a 3D microfluidic model. Our results demonstrate that 150–200 nm sEVs expressing CD63, CD9, and CD81 from brain organoid media decrease MDA-MB-231 cell proliferation, enhance their wound-healing capacity, alter their morphology into more mesenchymal mode, and increase their stemness. BO-sEVs led to heightened PD-L1, CD49f, and vimentin levels of expression in MDA-MB-231 cells, suggesting an amplified immunosuppressive, stem-like, and mesenchymal phenotype. Furthermore, these sEVs also induced the expression of neural markers such as GFAP in carcinoma cells. The cytokine antibody profiling array also showed that BO-sEVs enhanced the secretion of MCP-1, IL-6, and IL-8 by MDA-MB-231 cells. Moreover, sEVs significantly enhance the migration and invasion of carcinoma cells toward brain organoids in a 3D organoid-on-a-chip system. Our findings emphasize the potential significance of metastatic site-derived sEVs as pivotal mediators in carcinoma progression and adaptation to the brain microenvironment, thereby unveiling novel therapeutic avenues.

Graphical abstract: Impact of brain organoid-derived sEVs on metastatic adaptation and invasion of breast carcinoma cells through a microphysiological system

Article information

Article type
Paper
Submitted
05 Apr 2024
Accepted
11 Jun 2024
First published
12 Jun 2024

Lab Chip, 2024,24, 3434-3455

Impact of brain organoid-derived sEVs on metastatic adaptation and invasion of breast carcinoma cells through a microphysiological system

H. Nazari, A. Cho, D. Goss, J. P. Thiery and M. Ebrahimi Warkiani, Lab Chip, 2024, 24, 3434 DOI: 10.1039/D4LC00296B

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