RESEARCH ARTICLE


CXCR4-containing Exosomes Derived From Cancer Associated Fibroblasts Promote Epithelial Mesenchymal Transition in Ovarian Clear Cell Carcinoma



Fang Zhang1, *, Liang Chen2, *, Huijuan Li3, Naifu Liu2, Xinxin Zhang2, Jingwei Peng2, Jinlong Chen2, #
1 Department of Radiology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, P.R, China
2 Department of Gynecological Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, P. R. China
3 Department of Clinical Experiment, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, P. R. China


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Creative Commons License
© 2022 Fang et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Department of Gynecological Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, P. R. China; E-mail: jinlongchen90@126.com
#These authors contributed equally


Abstract

Aims:

Interaction between CAFs and OCCC in the tumor microenvironment and its possible pathway.

Background:

Ovarian clear cell carcinoma (OCCC) has high invasion, metastasis and poor prognosis. Tumor invasion is facilitated by epithelial mesenchymal transition (EMT), which is associated with stromal cells of tumors that mostly consist of cancer associated fibroblasts (CAFs). Exosomes are important carriers of information exchange and transmission between cells.

Objective:

We aimed to investigate whether CAFs can induce OCCC invasion through exosomes.

Methods:

We extracted exosomes with an exosome extraction kit. Immunofluorescence staining was used to detect whether exosomes were internalized by ES2 cells. EMT-related proteins were detected, and invasion experiments were carried out to investigate whether CAFs can induce OCCC invasion through exosomes.

Results:

We found that CAF and NF exosomes could be internalized in ES2 cells. The expression of OCCC CXCR4 protein could be increased by adding the supernatant of CAFs, but there was no significant change in the expression of CXCR4 mRNA. CXCR4 protein expression in CAF exosomes was significantly higher than that in NFs. Enhanced tumor invasiveness in ES2 cells was associated with CAF exosome-mediated, increased levels of N-cadherin and β-Catenin. Inhibition of CXCR4 expression or the Wnt/β-Catenin pathway of ES2 cells potentially reverses EMT and invasion induced by CAF exosomes.

Conclusion:

This study demonstrates that CXCR4-containing exosomes derived from CAFs could promote the EMT and invasion of OCCC.

Keywords: CAFs, CXCR4, OCCC, Exosomes, EMT, Invasion.