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Six-transmembrane epithelial antigen of the prostate 1 expression promotes ovarian cancer metastasis by aiding progression of epithelial-to-mesenchymal transition

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Abstract

Ovarian cancer is a severe malignant tumour of the female genital organs. Six-transmembrane epithelial antigen of the prostate 1 (STEAP1) expression is correlated with the occurrence and progression of multiple cancers. Here, we assessed STEAP1 expression in ovarian cancer and explored the relationship between STEAP1 and ovarian cancer progression. We used immunohistochemistry and public databases to test STEAP1 expression in normal human ovarian tissues, benign ovarian tumours, and ovarian cancer. The expression of STEAP1 and epithelial-to-mesenchymal transition (EMT)-related genes was analysed using immunocytochemistry, quantitative reverse transcription polymerase chain reaction, and western blotting in ovarian cancer cell lines. Lentivirus was used to knockdown and overexpress STEAP1. Invasion, migration, growth, clonogenicity, and apoptosis were assessed using transwell assay, growth curve, plate clone formation assay, and flow cytometry. We used a tumour xenograft to verify the relationship between STEAP1 and in vivo ovarian cancer cell growth. Matrix metalloproteinase-2 (MMP2) and matrix metalloproteinase-9 (MMP9) activities were examined using Matrix metalloproteinase zymography assay. STEAP1 was highly expressed in the human ovarian cancer tissues and a highly invasive ovarian cancer cell line. Overexpression of STEAP1 was related to poor prognosis in ovarian cancer patients. Down-regulation of STEAP1 suppressed the invasion, migration, proliferation, clonogenicity, EMT progression in human ovarian cancer cells and xenograft tumour growth in vivo, but it enhanced apoptosis. In human ovarian cancer, the STEAP1 gene is highly expressed, and its function is correlated with human ovarian cancer cell metastasis and growth. STEAP1 may be a possible target for suppressing ovarian cancer metastasis.

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Acknowledgements

Our study was funded by Nature Science Foundation of Shandong Province (ZR2017MH060) and Key R&D Plan of Shandong Province (2018GSF118049). These funds provided only financial support and were not involved in the study or manuscript writing.

Funding

This study was funded by the Nature Science Foundation of Shandong Province (ZR2017MH060) and Key R&D Plan of Shandong Province (2018GSF118049).

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Correspondence to Jie Chen.

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All authors in this study declare that they have no conflict of interests.

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This study was approved by the Medical Ethics Committee of Human and Animal Institution of Shandong University. All methods were performed in accordance with the relevant guidelines and regulations.

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We obtained the written informed consents of the patients involved in the study. All mouse experimental procedures were performed in accordance with the Regulations for the Administration of Affairs Concerning Experimental Animals approved by the State Council of the People’s Republic of China.

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Jiao, Z., Huang, L., Sun, J. et al. Six-transmembrane epithelial antigen of the prostate 1 expression promotes ovarian cancer metastasis by aiding progression of epithelial-to-mesenchymal transition. Histochem Cell Biol 154, 215–230 (2020). https://doi.org/10.1007/s00418-020-01877-7

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  • DOI: https://doi.org/10.1007/s00418-020-01877-7

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