@article{4321,
  author = {Hojjatollah Nazari and Ann-Na Cho and Dale Goss and Jean Paul Thiery and Majid Ebrahimi Warkiani},
  title = {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.},
  year = {2024},
  journal = {Lab on a Chip},
  volume = {24},
  pages = {3434-3455},
  month = {2024-07-10},
  issn = {1473-0189},
  url = {https://pubs.rsc.org/en/content/articlelanding/2024/lc/d4lc00296b},
  doi = {10.1039/D4LC00296B},
  language = {en},
}