Gene expression profiling of mouse breast tumor tissue after injection of 4T1 therapy-induced senesence derived sEVs
TNBC, associated with poor prognosis and high tumour recurrence, are often treated with anti-mitotic drugs. However, cells may bypass treatment-induced cell death via mitotic slippage, resulting in multinucleated polyploid cells and senescence activation. Senescent cancer cells represent a population of residual disease and are highly secretory. The SASP elicited is enriched in soluble cytokines linked to tumor recurrence and distant metastasis. In contrast, sEVs derived from senescent cancer cells represent an underappreciated aspect of SASP and its mechanistic role in mediating paracrine effects remains poorly-understood. Here, we show senescent sEVs as a distinct population of SASP that could elicit anti-tumor activity. Overall design: To investigate the effect of sEVs from therapy induced senescent breast cancer cells on mouse tumour growth, we have intratumourally injected Saline, Cont sEV and TIS sEV isolated from DMSO or 100 ng/ml Nocodozole treated 4T1 mouse breast cancer cells into the orthotopic BALB/c breast tumor mouse. Gene expression profiling analysis were performed using data obtained from RNA-seq of 3 different conditions (tumour tissue) after sEV treatment to orthotopic breast tumour mice. Comparative gene expression profiling analysis of RNA-seq data from mouse tumour tissue (Saline, Cont sEV, TIS sEV)