Identifying Signatures of EV Secretion in Metastatic Breast Cancer Through Functional Single-cell Profiling

Overview

Journal iScience

Publisher Cell Press

Date 2023 Apr 24

PMID 37091228

Authors

Mohsen Fathi

Melisa Martinez-Paniagua

Ali Rezvan

Melisa J Montalvo

Vakul Mohanty

Ken Chen

Sendurai A Mani

Navin Varadarajan

Affiliations

Soon will be listed here.

Abstract

Extracellular vesicles (EVs) regulate the tumor microenvironment by facilitating transport of biomolecules. Despite extensive investigation, heterogeneity in EV secretion among cancer cells and the mechanisms that support EV secretion are not well characterized. We developed an integrated method to identify individual cells with differences in EV secretion and performed linked single-cell RNA-sequencing on cloned single cells from the metastatic breast cancer cells. Differential gene expression analyses identified a four-gene signature of breast cancer EV secretion: , , , and . We functionally validated this gene signature by testing it across cell lines with different metastatic potential . Analysis of the TCGA and METABRIC datasets showed that this signature is associated with poor survival, invasive breast cancer types, and poor CD8 T cell infiltration in human tumors. We anticipate that our method for directly identifying the molecular determinants of EV secretion will have broad applications across cell types and diseases.

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