Exosomal ANXA2 derived from ovarian cancer cells regulates epithelial-mesenchymal plasticity of human peritoneal mesothelial cells.

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.

• Authors: Lingling Gao, Xin Nie, Rui Gou, Yuexin Hu, Hui Dong, Xiao Li, Bei Lin
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 25 Issue 23 Pg. 10916-10929 (12 2021) ISSN: 1582-4934 [Electronic] England
• PMID: 34725902 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

Chemical References

• ANXA2 protein, human
• Annexin A2

Topics

• Annexin A2 (genetics)
• Carcinoma, Ovarian Epithelial (genetics, pathology)
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• Epithelial-Mesenchymal Transition (genetics)
• Epithelium (pathology)
• Exosomes (genetics)
• Female
• Gene Expression Regulation, Neoplastic (genetics)
• Humans
• Ovarian Neoplasms (genetics, pathology)
• Peritoneum (pathology)
• Phosphatidylinositol 3-Kinases (genetics)
• Signal Transduction (genetics)
• Tumor Microenvironment (genetics)