Placental extracellular vesicles induce ovarian tumour cell death in an ex vivo explant model: Possible therapeutic potential

Abstract

Introduction: Placental extracellular vesicles (EVs), lipid-enclosed particles released from the placenta, can facilitate intercellular communication and are classified as micro- or nano-EVs depending on size. Placental EVs contain molecules associated with cell proliferation and death. In this study, we investigated whether treating human ovarian tumour explants with placental EVs could induce ovarian tumour cell death.

Methods: Human ovarian tumours were collected. After directly treating human ovarian tumour explants with placental EVs, cellular necrosis was observed in ovarian tumour explants by HE stains. Cell death-associated miRNAs were measured.

Results: Expression of apoptosis and senescence-associated proteins, including NF-κβ and γ H2AX, were significantly increased, while proliferation-associated proteins were significantly reduced in the explants after exposure to placental EVs. Furthermore, miRNA-519a-5p, miRNA-512-3p and miRNA-143-3p, which were reported to promote ovarian cancer cell apoptosis or inhibition of ovarian cancer cell growth, were significantly increased, and the target genes of miRNA-519a-5p and miRNA-512-3p were significantly reduced in the explants after exposure to placental EVs. Transfection of SK-OV-3 ovarian cancer cells with a mimic of miRNA-519a-5p or miRNA-143-3p reduced the viability of these cells.

Discussion: Our study demonstrated that placental EVs could induce necrosis in ovarian tumour explants. Increased levels of apoptosis and senescence-associated proteins and miRNAs could contribute to this change in ovarian tumour cell phenotype after exposure to placental EVs.

Keywords: Necrosis; Ovarian cancer; Placental extracellular vesicles; miRNAs.