Stanniocalcin 1 in tumor microenvironment promotes metastasis of ovarian cancer
Authors Yang Y, Yin S, Li S, Chen Y, Yang L
Received 27 November 2018
Accepted for publication 6 March 2019
Published 11 April 2019 Volume 2019:12 Pages 2789—2798
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Andrew Yee
Peer reviewer comments 3
Editor who approved publication: Dr Leo Jen-Liang Su
Yuqi Yang,1 Sheng Yin,2 Shuqing Li,3 Yaping Chen,1 Lina Yang1
1Department of Obstetrics and Gynecology, The Fifth People’s Hospital of Shanghai, Fudan University, Shanghai, People’s Republic of China; 2Department of Obstetrics and Gynecology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 3Obstetrics and Gynecology Hospital of Fudan University, Shanghai, People’s Republic of China
Background: Tumor metastasis is the major challenge for ovarian cancer treatment. Cancer-associated fibroblasts (CAFs), a major component existing in tumor microenvironment, can secrete several cytokines to interact with cancer epithelial cells, and promote cancer metastasis. Stanniocalcin 1 (STC1), a secretory glycoprotein hormone, has been proven to be an important factor in ovarian tumorigenesis.
Methods: In this study, we focused on the functional role of STC1 in ovarian cancer microenvironment, investigated STC1’s effects on the proliferation and metastasis of ovarian cancer cells, and explored the molecular mechanism underlying STC1-mediated cancer metastasis.
Results: By analyzing the GEO dataset and examined STC1 expression in CAFs isolated from ovarian cancer patients, we found that expression of STC1 was higher in ovarian cancer stroma and CAFs than in the normal ovarian stroma and normal fibroblasts (NFs). Addition of recombinant human STC1 (rhSTC1) promoted cell proliferation and metastasis in ovarian cancer, while adoption of STC1 neutralizing antibody (STC1 Ab) abolished the effects. Furthermore, our results revealed that STC1 promoted the phosphorylation of Akt (Ser473), and upregulated several epithelial–mesenchymal transition (EMT) markers including fibronectin，vimentin and slug. In addition, we demonstrated that STC1 in tumor microenvironment could mediate the conversion of NFs to CAFs.
Conclusion: Taken together, the study results suggested the crucial role of STC1 in tumor environment on the metastasis of ovarian cancer.
Keywords: STC1, tumor microenvironment, CAFs, EMT, metastasis
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