Abstract
Purpose
Stroma-derived factor-1 (SDF-1) and its receptor C-X-C chemokine receptor-4 (CXCR4) are involved in human endometrial carcinoma (EC) progression. CXCR7 is another important receptor of SDF-1 and has a higher affinity with SDF-1 compared with that of CXCR4. This paper aims to study the effects of the SDF-1/CXCR7 axis on the growth and invasion ability of EC cells.
Methods
CXCR7 expression was evaluated by quantitative RT-PCR, immunohistochemistry, immunocytochemistry and Western blotting in EC cell lines and 30 cases of primary EC tissue from patients. EC cell line proliferation and migration were assessed following knockdown of CXCR7 by MTT and transwell assays.
Results
The results showed that CXCR7 was highly expressed at both mRNA and protein levels in the EC cells and tissue. siCXCR7 effectively silenced CXCR7 in Ishikawa and AN3CA cells. Treatment with 17β-oestradiol (17β-E2) significantly increased the levels of CXCR7 and SDF-1 in Con, siCon and siCXCR7 treated Ishikawa. siCXCR7 persistently inhibited CXCR7 expression, even in cells treated with 17β-E2. Moreover, in vitro functional analyses, silencing CXCR7 resulted in decreased proliferation in Ishikawa and AN3CA cells. Treatment with 17β-E2 and SDF-1 significantly promoted the growth and migration in siCon treated Ishikawa and AN3CA. Interestingly, in response to 17β-E2 and SDF-1 stimulation, siCXCR7 continuously inhibited the growth and invasion of Ishikawa and AN3CA cells.
Conclusion
Our results indicate that SDF-1/CXCR7 plays a positive role in the proliferation and invasion of EC cells. CXCR7 inhibition treatment may provide a promising strategy for anti-tumour therapy for EC.
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Acknowledgements
This work was supported by the National Natural Sciences Foundation of China (No. 81001154).
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This article contains tissue from human participants. All of the procedures performed in studies involving human participants were in accordance with the ethical standards of the Institute Research Ethics Committee of Shanghai first people’s hospital and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Informed consent was obtained from all of the individual participants included in the study.
Authors’ contributions
Hong-qin Gu: Project development, manuscript writing. Zhen-bo Zhang, Jia-wen Zhang: Data collection or management. Qian–qian Wang: Data analysis. Xiao-wei Xi, Yin-yan He: Protocol/project development.
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Gu, Hq., Zhang, Zb., Zhang, Jw. et al. The role of the SDF-1/ CXCR7 axis on the growth and invasion ability of endometrial cancer cells. Arch Gynecol Obstet 295, 987–995 (2017). https://doi.org/10.1007/s00404-017-4308-x
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DOI: https://doi.org/10.1007/s00404-017-4308-x