Exosomal Metastasis‑Associated Lung Adenocarcinoma Transcript 1 Promotes Angiogenesis and Predicts Poor Prognosis in Epithelial Ovarian Cancer

• Published in: International journal of biological sciences Vol. 14; no. 14; pp. 1960 - 1973
• Main Authors: Qiu, Jun-Jun, Lin, Xiao-Jing, Tang, Xiao-Yan, Zheng, Ting-Ting, Lin, Ying-Ying, Hua, Ke-Qin
• Format: Journal Article
• Language: English
• Published: Australia Ivyspring International Publisher Pty Ltd 01.01.2018; Ivyspring International Publisher
• Subjects: Adenocarcinoma; Angiogenesis; Animals; Biomarkers; Blotting, Western; Calibration; Cancer; Carcinoma, Ovarian Epithelial - genetics; Carcinoma, Ovarian Epithelial - pathology; Confidence intervals; Crosstalk; Data processing; Endothelial cells; Exosomes; Exosomes - genetics; Exosomes - metabolism; Female; Gene expression; Human Umbilical Vein Endothelial Cells; Humans; Immunohistochemistry; Lungs; Medical prognosis; Metastases; Metastasis; Mice, Inbred BALB C; Mice, Nude; Microscopy, Electron, Transmission; Multivariate Analysis; Neovascularization, Pathologic - genetics; Neovascularization, Pathologic - metabolism; Nomograms; Ovarian cancer; Phenotypes; Predictions; Prognosis; Real-Time Polymerase Chain Reaction; Research Paper; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Statistical analysis; Transcription; Umbilical vein; intercellular communication; lncRNA; exosome; prognosis; angiogenesis
• ISSN: 1449-2288; 1449-2288
• DOI: 10.7150/ijbs.28048

Exosomes mediate cell-cell crosstalk in cancer progression by transferring their molecular cargos, including long noncoding RNAs (lncRNAs). Metastasis‑associated lung adenocarcinoma transcript 1 (MALAT1) is a well-known lncRNA associated with cancer angiogenesis and metastasis. However, the presence of MALAT1 in exosomes and the roles and clinical values of exosomal MALAT1 in epithelial ovarian cancer (EOC) remain unknown. The present study focused on the crosstalk between EOC cells and endothelial cells mediated by exosomal MALAT1 and aimed to explore the roles of exosomes and exosomal MALAT1 in EOC angiogenesis and to reveal the clinical relevance and prognostic predictive value of serum exosomal MALAT1 in EOC. We observed that MALAT1 was increased in both metastatic EOC cells and their secreted exosomes. Exosomal MALAT1 derived from EOC cells was transferred to recipient human umbilical vein endothelial cells (HUVECs) via exosomes. In vitro and in vivo experiments demonstrated that MALAT1 knockdown impaired the exosome-mediated proangiogenic activity of HUVECs through certain key angiogenesis-related genes. Clinically, elevated serum exosomal MALAT1 was highly correlated with an advanced and metastatic phenotype of EOC and was an independent predictive factor for EOC overall survival (OS). Moreover, a prognostic nomogram model we constructed showed a good prediction of the probability of 3-year OS of EOC patients according to the c-index (0.751, 95% confidence interval [CI]=0.691-0.811) and calibration curve. Collectively, our data provide a novel mechanism by which EOC cells transfer MALAT1 via exosomes to recipient HUVECs and influence HUVECs by stimulating angiogenesis-related gene expression, eventually promoting angiogenesis. Additionally, circulating exosomal MALAT1 can serve as a promising serum-based, noninvasive predictive biomarker for EOC prognosis.