Plasma cells shape the mesenchymal identity of ovarian cancers through transfer of exosome-derived microRNAs
Open Access
- 26 February 2021
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Advances
- Vol. 7 (9), eabb0737
- https://doi.org/10.1126/sciadv.abb0737
Abstract
Ovarian cancer represents a highly lethal disease that poses a substantial burden for females, with four main molecular subtypes carrying distinct clinical outcomes. Here, we demonstrated that plasma cells, a subset of antibody-producing B cells, were enriched in the mesenchymal subtype of high-grade serous ovarian cancers (HGSCs). Plasma cell abundance correlated with the density of mesenchymal cells in clinical specimens of HGSCs. Coculture of nonmesenchymal ovarian cancer cells and plasma cells induced a mesenchymal phenotype of tumor cells in vitro and in vivo. Phenotypic switch was mediated by the transfer of plasma cell–derived exosomes containing miR-330-3p into nonmesenchymal ovarian cancer cells. Exosome-derived miR-330-3p increased expression of junctional adhesion molecule B in a noncanonical fashion. Depletion of plasma cells by bortezomib reversed the mesenchymal characteristics of ovarian cancer and inhibited in vivo tumor growth. Collectively, our work suggests targeting plasma cells may be a novel approach for ovarian cancer therapy.Keywords
Funding Information
- National Institutes of Health (CA217065)
- National Natural Science Foundation of China (81822034)
- National Natural Science Foundation of China (81821002)
- National Natural Science Foundation of China (81773119)
- Graduate Student’s Research and Innovation Fund of Sichuan University (2018YJSY117)
- National Key Research and Development Program of China Stem Cell and Translational Research (2017YFA0106800)
- National Key Research and Development Program of China Stem Cell and Translational Research (2018YFA0109200)
- Direct Scientific Research Grants from West China Second Hospital, Sichuan University (KS021)
- Direct Scientific Research Grants from West China Second Hospital, Sichuan University (K1907)
- Sichuan Science-Technology International Cooperation Project (2019YFH0144)
- Research Grants Council of the Hong Kong Special Administrative Region, China (CityU 11103718)
- NIH grants (CA197718)
- NIH grants (CA154130)
- NIH Grant (CA169117)
- NIH Grant (CA171652)
- NIH Grant (NS087913)
- NIH Grant (NS089272)
This publication has 57 references indexed in Scilit:
- Functional genomics identifies five distinct molecular subtypes with clinical relevance and pathways for growth control in epithelial ovarian cancerEMBO Molecular Medicine, 2013
- Prognostically relevant gene signatures of high-grade serous ovarian carcinomaJCI Insight, 2012
- STAR: ultrafast universal RNA-seq alignerBioinformatics, 2012
- miR-141 and miR-200a act on ovarian tumorigenesis by controlling oxidative stress responseNature Medicine, 2011
- Integrated genomic analyses of ovarian carcinomaNature, 2011
- Regulation of mRNA Translation and Stability by microRNAsAnnual Review of Biochemistry, 2010
- Novel Molecular Subtypes of Serous and Endometrioid Ovarian Cancer Linked to Clinical OutcomeClinical Cancer Research, 2008
- A Gene Signature Predicting for Survival in Suboptimally Debulked Patients with Ovarian CancerCancer Research, 2008
- GEOquery: a bridge between the Gene Expression Omnibus (GEO) and BioConductorBioinformatics, 2007
- Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profilesProceedings of the National Academy of Sciences of the United States of America, 2005