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Exosomal ANXA2 derived from ovarian cancer cells regulates epithelial-mesenchymal plasticity of human peritoneal mesothelial cells |
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| Authors: | Lingling Gao Xin Nie Rui Gou Yuexin Hu Hui Dong Xiao Li Bei Lin |
| Institution: | 1. Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
Key Laboratory of Maternal-Fetal Medicine of Liaoning Province, Key Laboratory of Obstetrics and Gynecology of Higher Education of Liaoning Province, Shenyang, China Contribution: Formal analysis (lead), Investigation (lead), Methodology (lead), Resources (lead), Validation (lead), Writing - original draft (lead), Writing - review & editing (lead);2. Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China Key Laboratory of Maternal-Fetal Medicine of Liaoning Province, Key Laboratory of Obstetrics and Gynecology of Higher Education of Liaoning Province, Shenyang, China Contribution: Data curation (equal), Investigation (equal), Supervision (equal);3. Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China;4. Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China Key Laboratory of Maternal-Fetal Medicine of Liaoning Province, Key Laboratory of Obstetrics and Gynecology of Higher Education of Liaoning Province, Shenyang, China Contribution: Investigation (equal), Validation (equal);5. Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China Key Laboratory of Maternal-Fetal Medicine of Liaoning Province, Key Laboratory of Obstetrics and Gynecology of Higher Education of Liaoning Province, Shenyang, China Contribution: Investigation (supporting), Writing - original draft (supporting);6. Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China Key Laboratory of Maternal-Fetal Medicine of Liaoning Province, Key Laboratory of Obstetrics and Gynecology of Higher Education of Liaoning Province, Shenyang, China Contribution: Data curation (supporting), Visualization (supporting) |
| Abstract: | Ovarian cancer, one of the malignant gynaecological tumours with the highest mortality rate among female reproductive system, is prone to metastasis, recurrence and chemotherapy resistance, causing a poor prognosis. Exosomes can regulate the epithelial-mesenchymal plasticity of tumour cells, remodel surrounding tumour microenvironment, and affect tumour cell proliferation, invasion and metastasis. However, the function and mechanism of exosomes in the intraperitoneal implantation of ovarian cancer remain unclear. In this study, exosomal annexin A2 (ANXA2) derived from ovarian cancer cells was co-cultured with human peritoneal mesothelial (HMrSV5) cells; functional experiments were conducted to explore the effects of exosomal ANXA2 on the biological behaviour of HMrSV5 and the related mechanisms. This study showed that ANXA2 in ovarian cancer cells can be transferred to HMrSV5 cells through exosomes, exosomal ANXA2 can not only promote the migration, invasion and apoptosis of HMrSV5 cells, but also regulates morphological changes and fibrosis of HMrSV5 cells. Furthermore, ANXA2 promotes the mesothelial-mesenchymal transition (MMT) and degradation of the extracellular matrix of HMrSV5 cells through PI3K/AKT/mTOR pathway, finally affects pre-metastasis microenvironment of ovarian cancer, which provides a new theoretical basis for the mechanism of intraperitoneal implantation and metastasis of ovarian cancer. |
| Keywords: | ANXA2 epithelial-mesenchymal plasticity exosome Implantation and metastasis ovarian cancer |