RT Journal Article
SR Electronic
T1 Role of extracellular vesicles in chemotherapy-induced lung metastasis
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 3944
DO 10.1183/13993003.congress-2020.3944
VO 56
IS suppl 64
A1 Nahal Mansouri
A1 Ioanna Keklikoglou
A1 Sina Nassiri
A1 Bruno Torchia
A1 Alan Guichard
A1 Michele De Palma
YR 2020
UL http://erj.ersjournals.com/content/56/suppl_64/3944.abstract
AB Introduction: Chemoresistant tumors face a high risk of metastatic disease. Recent work suggest that certain forms of chemotherapy induce systemic host responses that may facilitate metastasis from chemoresistant mammary tumors. We have shown that chemotherapy induces mammary cancer cells to release extracellular vesicles (EVs) with altered protein composition and enhanced pro-metastatic capacity. Identifying and blocking the mechanisms that promote chemotherapy-induced lung metastasis may improve treatment efficacy in breast cancer patients receiving neoadjuvant chemotherapy.Objectives: We profiled the proteomes and studied the effects of chemotherapy-induced, tumor-derived EVs on the mouse pulmonary niche.Methods: The proteomes of EVs isolated from paclitaxel (chemo-EVs) or vehicle-treated (control-EVs) 4T1 mouse mammary tumor cells were analysed using mass spectrometry. Tumor-free mice were injected with 3 doses of chemo-EVs or control-EVs and the lung tissue was analysed by single-cell RNA sequencing. Canonical marker genes were used for cell type annotation and differential gene expression was analysed in each cell cluster.Results: Mass spectrometry analysis revealed the abundance of multiple pro-metastatic proteins in chemo-EVs. Single-cell RNA sequencing revealed differential gene expression in chemo-EV versus control-EV–treated mice, some of which may be associated with progression of metastasis.Conclusions: We comprehensively profiled the proteome of EVs released from chemotherapy-treated cancer cells, and the transcriptome of the lung tissue exposed to chemotherapy at the single cell level. This work may help identify molecular pathways relevant to chemotherapy-induced metastasis.FootnotesCite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 3944.This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).