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Exosomal Integrin α5β1/AEP Complex Derived from EOC Promotes Peritoneal Metastasis Through Regulating Mesothelial Cells Proliferation and Migration
31 Pages Posted: 15 Jun 2019
More...Abstract
Purpose: Epithelial ovarian cancer (EOC) is one of the most malignant cancer in gynecologic system. Many patients are diagnosed at advanced stage with widely disseminated intra-peritoneal metastasis. EOC spreads via direct extension and transcoelomic spread. However, the interplay between human peritoneal mesothelial cells (HPMCs) and EOC cells is ambiguous. we hypothesize that integrin in HPMCs plays an important role in tumor initial metastasis. Experimental.
Design: The expression of integrin different subtypes from HPMCs was validated using WB. The integrin α5β1 high expression and colocalization with asparaginyl endopeptidase (AEP) in EOC cells and HPMCs derived from EOC patients (EOC-HPMCs) was concluded by IF. The role and mechanism of exosomal integrin α5β1/AEP complex in HPMCs was elucidated using in vitro and in vivo. A retrospective study involving 234 patients showed levels of integrin α5β1/AEP in circulating serum and ascites of EOCs patients, and the association between integrin α5β1/AEP expression and overall survival.
Results: The integrin α5β1 was highly expressed and co-localized with AEP in EOC cells, and exosomal integrin α5β1/AEP complex secreted by EOC cells played an important role in the proliferation and migration of HPMCs. High levels of exosomal integrin α5β1/AEP were also found in circulating serum and ascites of EOCs patients, and the expression of integrin α5β1/AEP in EOC tissues was negatively associated with overall survival.
Conclusions: EOC regulated the function of HPMCs through exosomal integrin α5β1/AEP, which might be crucial for EOC peritoneal initial metastasis.
Funding Statement: This study was supported by grants from the National Science Foundation of China (81372787, 81402042, 81602280), Shanghai Municipal Health Bureau (20154Y0109), Shanghai Science and Technology Development Foundation (17411968100), and the Training plan for scientific research of Renji Hospital (RJZZ13-021).
Declaration of Interests: The authors have declared that no conflict of interest exists.
Ethics Approval Statement: The study protocol was reviewed and approved by the Institutional Review Board of Shanghai First Maternity and Infant Hospital, in accordance with the Declaration of Helsinki.
Keywords: EOC, integrin α5β1, AEP, HPMC, peritoneal metastasis
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