Chemotherapy-Induced Upregulation of Small Extracellular Vesicle-Associated PTX3 Accelerates Breast Cancer Metastasis.

ABSTRACT: Although neoadjuvant chemotherapy is a standard component of breast cancer treatment, recent evidence suggests that chemotherapeutic drugs can promote metastasis through poorly defined mechanisms. Here we utilize xenograft mouse models of triple-negative breast cancer to explore the importance of chemotherapy-induced tumor-derived small extracellular vesicles (sEV) in metastasis. Doxorubicin (DXR) enhanced tumor cell sEV secretion to accelerate pulmonary metastasis by priming the premetastatic niche. Proteomic analysis and CRISPR/Cas9 gene editing identified the inflammatory glycoprotein PTX3 enriched in DXR-elicited sEV as a critical regulator of chemotherapy-induced metastasis. Both genetic inhibition of sEV secretion from primary tumors and pharmacologic inhibition of sEV uptake in seco

SUBMITTER: Wills CA 

PROVIDER: S-EPMC7855036 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature