The Exosomal Integrin α5β1/AEP Complex Derived from Epithelial Ovarian Cancer Cells Promotes Peritoneal Metastasis Through Regulating Mesothelial Cell Proliferation and Migration

Overview

Journal Cell Oncol (Dordr)

Publisher Springer

Date 2020 Feb 22

PMID 32080801

Citations 29

Authors

Xiaoduan Li

Meiling Tang

Qinyi Zhu

Xinjing Wang

Yingying Lin

Xipeng Wang

Affiliations

Soon will be listed here.

Abstract

Purpose: Epithelial ovarian cancer (EOC) is one of the most malignant cancers in the gynecologic system. Many patients are diagnosed at an advanced stage with disseminated intra-peritoneal metastases. EOC spreads via both direct extension and trans-coelomic spread. However, the interplay between human peritoneal mesothelial cells (HPMCs) and EOC cells is still ambiguous. We hypothesize that integrins (ITG) in HPMCs may play important roles in EOC metastasis.

Methods: The expression of different integrin subtypes from HPMCs was assessed using Western blotting. The expression of integrin α5β1 (ITGA5B1) and its co-localization with asparaginyl endopeptidase (AEP) in HPMCs derived from EOC patients (EOC-HPMCs) were assessed using immunofluorescence. The role and mechanism of the exosomal ITGA5B1/AEP complex in HPMCs was assessed using both in vitro and in vivo assays. A retrospective study involving 234 cases was carried out to assess ITGA5B1 and AEP levels in circulating sera and ascites of EOC patients, as well as associations between ITGA5B1/AEP expression and overall survival.

Results: We found that ITGA5B1was highly expressed and co-localized with AEP in EOC cells, and that the exosomal ITGA5B1/AEP complex secreted by EOC cells played an important role in the proliferation and migration of HPMCs. High levels of exosomal ITGA5B1/AEP were also found in circulating sera and ascites of EOC patients, and the expression of ITGA5B1/AEP in EOC tissues was found to be negatively associated with overall survival.

Conclusions: Our data indicate that EOCs may regulate the function of HPMCs through exosomal ITGA5B1/AEP, which may be crucial for peritoneal metastasis.

Citing Articles

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Gu H, Li Q, Liu Z, Li Y, Liu K, Kong X Adv Sci (Weinh). 2024; 12(7):e2411162.

PMID: 39721032 PMC: 11831503. DOI: 10.1002/advs.202411162.

Exosomes: Key Factors in Ovarian Cancer Peritoneal Metastasis and Drug Resistance.

Shao M, Gao Y, Xu X, Chan D, Du J Biomolecules. 2024; 14(9).

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Unraveling the extracellular vesicle network: insights into ovarian cancer metastasis and chemoresistance.

Dai W, Zhou J, Chen T Mol Cancer. 2024; 23(1):201.

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Platinum-induced upregulation of ITGA6 promotes chemoresistance and spreading in ovarian cancer.

Gambelli A, Nespolo A, Rampioni Vinciguerra G, Pivetta E, Pellarin I, Nicoloso M EMBO Mol Med. 2024; 16(5):1162-1192.

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A decrease in integrin α5β1/FAK is associated with increased apoptosis of aortic smooth muscle cells in acute type a aortic dissection.

Xue M, Xing L, Yang Y, Shao M, Liao F, Xu F BMC Cardiovasc Disord. 2024; 24(1):180.

PMID: 38532364 PMC: 10964683. DOI: 10.1186/s12872-024-03778-2.

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