Serum Exosomes From Epithelial Ovarian Cancer Patients Contain LRP1, Which Promotes the Migration of Epithelial Ovarian Cancer Cell

• Published in: Molecular & cellular proteomics Vol. 22; no. 4; p. 100520
• Main Authors: Zhou, Wei, Ma, Jiachen, Zhao, Han, Wang, Qing, Guo, Xiaoli, Chen, Linna, Cao, Zhonghui, Xu, Jiahao, Zhang, Bei, Zhou, Xueyan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2023; American Society for Biochemistry and Molecular Biology
• Subjects: Carcinoma, Ovarian Epithelial; Cell Line, Tumor; epithelial ovarian cancer; exosome; Exosomes - metabolism; Female; Humans; Low Density Lipoprotein Receptor-Related Protein-1 - metabolism; low-density lipoprotein receptor-related protein 1; migration; Ovarian Neoplasms - pathology; Proteomics; Signal Transduction; proteomics; LRP1; GO; PPI; DEP; low-density lipoprotein receptor-related protein 1; MMP; OC; migration; EOC; epithelial ovarian cancer; exosome; TEM
• ISSN: 1535-9476; 1535-9484
• DOI: 10.1016/j.mcpro.2023.100520

Ovarian cancer is a gynecological tumor with extremely high mortality and poor prognosis. Exosomes derived from tumor cells contain abundant proteins that may influence tumor metastasis. The purpose of our study was to explore the proteomic profile of serum exosomes from epithelial ovarian cancer (EOC) patients and to find potential diagnostic markers for EOC. We obtained purified exosomes from serum using ultracentrifugation. Migration assay was used to evaluate the effects of exosomes on the migration of EOC cells. Proteomic profile of serum exosomes was analyzed by liquid chromatogram-tandem mass spectrometry. The levels of low-density lipoprotein receptor-related protein 1 (LRP1) in serum and serum exosomes were determined by enzyme-linked immunosorbent assay. Western blot and Immunohistochemistry were used to determine the level of LRP1 in tissues. Moreover, we performed small-interfering RNA-mediated knockdown of LRP1 in EOC cells to obtain SI-LRP1-Exos and SI-NC-Exos. The detailed mechanisms by which exosomal LRP1 affected the migration of EOC cells in vitro and in vivo were also explored. We found that serum exosomes from EOC patients contributed to the migration of EOC cells. The level of serum exosomal LRP1 of EOC patients was significantly upregulated compared with that of healthy volunteers, which was consistent with the result of enzyme-linked immunosorbent assay. We found that exosomal LRP1 regulated the expression of MMP2 and MMP9 through ERK signaling pathway and affected the migration of EOC cells in vitro and in vivo. Therefore, we propose that exosomal LRP1 contributes to the migration of EOC and may act as an important diagnostic and prognostic biomarker of EOC. The levels of low-density lipoprotein receptor-related protein 1 were increased in exosomes from serum of epithelial ovarian cancer patients, exosomal low-density lipoprotein receptor-related protein 1 affected the migration of epithelial ovarian cancer cells through p-ERK/MMP2/MMP9 signaling pathway. [Display omitted] •Ovarian cancer is the deadliest gynecological malignancy.•Exosomes play a key role in mediating cancer metastasis.•Proteomic analysis of exosomes from serum.•Exosomal LRP1 may act as a marker of epithelial ovarian cancer. Ovarian cancer is the most lethal malignant gynecological tumor, and the clinical diagnosis and treatment of OC have always been difficult. Cancer cell–derived exosomes play a key role in mediating cancer progression. We performed proteomics analysis of serum exosomes to discover biomarkers for epithelial ovarian cancer.