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Sulfatase-1 knockdown promotes in vitro and in vivo aggressive behavior of murine hepatocarcinoma Hca-P cells through up-regulation of mesothelin

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Journal of Cell Communication and Signaling Aims and scope

Abstract

Our previous study (Oncotarget 2016; 7:46) demonstrated that the over-expression of sulfatase-1 in murine hepatocarcinoma Hca-F cell line (a murine HCC cell with lymph node metastatic [LNM] rate of >75%) downregulates mesothelin and leads to reduction in lymphatic metastasis, both in vitro and in vivo. In current work, we investigated the effects of Sulf-1 knockdown on mesothelin (Msln) and it’s effects on the in vitro cell proliferation, migration, invasion, and in vivo tumor growth and LNM rate for Hca-P cells (a murine HCC cell with LNM rate of <25%). Western blotting and qRT-PCR assay indicated that both in vitro and in vivo Sulf-1 was down-regulated by 75% and 68% and led to up regulation of Msln by 55% in shRNA-transfected-Sulf-1-Hca-P cells compared with Hca-P and nonspecific sequence control plasmid transfected Hca-P cell (shRNA-Nc-Hca-P). The in vitro proliferation, migration and invasion potentials were significantly enhanced following Sulf-1 stable down-regulation. In addition, Sulf-1 knock-down significantly promoted tumor growth and increased LNM rates of shRNA-Sulf-1-Hca-P-transplanted mice by 78.6% (11 out of 14 lymph nodes were positive of cancer). Consistent with our previous work, we confirmed that Sulf-1 plays an important role in hepatocarcinoma cell proliferation, migration, invasion and metastasis. The interaction between Sulf-1 and Msln is a potential therapeutic target in the development of liver cancer therapy.

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Funding

This work was supports by grants from the National Natural Science Foundation of China [No. 81071725 and No. 30772468]; and the Financial Department of Liaoning Province [Nos. 20,121,203]. We would like to thank the Department of Pathology and the Key Lab for Tumor Metastasis and Intervention of Liaoning Province, as well as, and the Chinese Scholarship Council (CSC).

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Authors and Affiliations

  1. Department of Pathology and Pathophysiology, Key laboratory for Tumor Metastasis and Intervention of Liaoning Province, Dalian Medical University, 9 west Lvshun Southern road, Dalian, Liaoning, 116044, China

    Salma Abdi Mahmoud, Mohammed Mohammed Ibrahim, Ahmed Hago Musa, Yuhong Huang, Jun Zhang, Jingwen Wang, Yuanyi Wei, Li Wang, Shunting Zhou, Boyi Xin, Wei Xuan & Jianwu Tang

  2. Department of Pathology, School of Medicine and Health Sciences, University for Development Studies, Tamale, Ghana

    Mohammed Mohammed Ibrahim

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  1. Salma Abdi Mahmoud
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  2. Mohammed Mohammed Ibrahim
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  3. Ahmed Hago Musa
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  4. Yuhong Huang
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  5. Jun Zhang
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Correspondence to Jianwu Tang.

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Mahmoud, S.A., Ibrahim, M.M., Musa, A.H. et al. Sulfatase-1 knockdown promotes in vitro and in vivo aggressive behavior of murine hepatocarcinoma Hca-P cells through up-regulation of mesothelin. J. Cell Commun. Signal. 12, 603–613 (2018). https://doi.org/10.1007/s12079-017-0411-9

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  • DOI: https://doi.org/10.1007/s12079-017-0411-9

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