Plasma cells shape the mesenchymal identity of ovarian cancers through transfer of exosome-derived microRNAs

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.

Tumor-Derived Extracellular Vesicles Regulate Cancer Progression in the Tumor Microenvironment

“…Relying on transferring microRNA (miRNA), long noncoding RNA (lncRNA), messenger RNA (mRNA) and proteins, EVs modulate the functions and phenotypes of target cells ( Bayraktar et al, 2017 ; Choi et al, 2017 ; Gon et al, 2017 ). For instance, the delivery of miR-330-3p from plasma cells to ovarian cancer cells by EVs induces a mesenchymal phenotype of ovarian cancers ( Yang et al, 2021 ). In addition, EVs isolated from human vascular endothelial cells contain some cardioprotective proteins, which contribute to promoting human myocardium survival after ischemia-reperfusion injury ( Yadid et al, 2020 ).…”

Nucleic acids and proteins carried by exosomes of different origins as potential biomarkers for gynecologic cancers

“…Plasma cells conferred the mesenchymal identity of ovarian cancers by enhancing the transfer of exosome-derived miR-330-3p. 62 Exosomal miR-98-5p from CAFs facilitated the proliferation and cell cycle entry and inhibited the apoptotic ability of ovarian cancer cells. 63 In summary, the different characteristics of exosomes in ovarian cancer development are predominantly determined by the cell types from which they originate.…”

Non-Coding RNAs Delivery by Small Extracellular Vesicles and Their Applications in Ovarian Cancer

“…Ascites-derived exosomal miR-6780b-5p promotes the epithelial–mesenchymal transition (EMT) of OC cells, a key step in the invasion and metastasis ( Cai et al, 2021 ). In addition, similar to epithelial cells that acquire fibroblast-like motility and phenotype in EMT, “mesothelial–mesenchymal transition” (MMT) refers to PMCs being converted into cancer-associated fibroblasts (CAFs) with a mesenchymal phenotype, which leads to tissue fibrosis and peritoneal adhesions ( Si et al, 2019 ; Yang Z. G. et al, 2021 ). The lncRNA SPOCD1-AS is derived from the sEVs of OC.…”