Oncotarget

Research Papers:

Overexpression of sulfatase-1 in murine hepatocarcinoma Hca-F cell line downregulates mesothelin and leads to reduction in lymphatic metastasis, both in vitro and in vivo

Salma Mahmoud, Mohammed Ibrahim, Ahmed Hago, Yuhong Huang, Yuanyi Wei, Jun Zhang, Qingqing Zhang, Yu Xiao, Jingwen Wang, Munkaila Adam, Yu Guo, Li Wang, Shuting Zhou, Boyi Xin, Wei Xuan and Jianwu Tang _

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Oncotarget. 2016; 7:75052-75063. https://doi.org/10.18632/oncotarget.11933

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Abstract

Salma Mahmoud1, Mohammed Ibrahim1,2, Ahmed Hago1, Yuhong Huang1, Yuanyi Wei1, Jun Zhang1, Qingqing Zhang1, Yu Xiao1, Jingwen Wang1, Munkaila Adam2, Yu Guo1, Li Wang1, Shuting Zhou1, Boyi Xin1, Wei Xuan1, Jianwu Tang1

1Department of Pathology, Dalian Medical University, Dalian 116044, China

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

Correspondence to:

Jianwu Tang, email: jianwutang@163.com

Keywords: sulfatase-1, mesothelin, hepatocellular carcinoma, migration and invasion, lymph node metastasis

Received: June 17, 2016    Accepted: August 26, 2016    Published: September 10, 2016

ABSTRACT

Lymphatic vessels function as transport channels for tumor cells to metastasize from the primary site into the lymph nodes. In this experiment we evaluated the effect of Sulfatase-1 (Sulf-1) on metastasis by upregulating it in murine hepatocarcinoma cell line Hca-F with high lymph node metastatic rate of >75%. The study in vitro showed that upregulation of Sulf-1 in Hca-F cells significantly reduced cell proliferation, migration and invasion (p<0.05). Also, the forced expression of Sulf-1 downregulated Mesothelin (Msln) at both the protein and mRNA levels. The experiment in vivo further showed that up-regulation of Sulf-1 with the attendant downregulation of mesothelin delayed tumor growth and decreased lymph node metastasis. In conclusion, our findings show that Sulf-1 is an important tumor suppressor gene in hepatocellular carcinoma (HCC), and its overexpression downregulates Msln and results in a decrease in HCC cell proliferation, migration, invasion, and lymphatic metastasis. This functional relationship between Sulf-1 and Msln could be exploited for the development of a novel liver cancer therapy.


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