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.
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 up regulation of Sulf-1 in Hca-F cells significantly reduced cell proliferation, migration and invasion (p<0.05). Also, the forced expression of Sulf-1 down regulated 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 over expression 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.
Department of Pathology, Dalian Medical University, Dalian 116044, China.
Salma
S
Mahmoud
Department of Pathology, Dalian Medical University, Dalian 116044, China.|Department of Pathology, School of Medicine and Health Sciences, University for Development Studies, Tamale, Ghana.
Mohammed
M
Ibrahim
Department of Pathology, Dalian Medical University, Dalian 116044, China.
Ahmed
A
Hago
Department of Pathology, Dalian Medical University, Dalian 116044, China.
Yuhong
Y
Huang
Department of Pathology, Dalian Medical University, Dalian 116044, China.
Yuanyi
Y
Wei
Department of Pathology, Dalian Medical University, Dalian 116044, China.
Jun
J
Zhang
Department of Pathology, Dalian Medical University, Dalian 116044, China.
Qingqing
Q
Zhang
Department of Pathology, Dalian Medical University, Dalian 116044, China.
Yu
Y
Xiao
Department of Pathology, Dalian Medical University, Dalian 116044, China.
Jingwen
J
Wang
Department of Pathology, School of Medicine and Health Sciences, University for Development Studies, Tamale, Ghana.
Munkaila
M
Adam
Department of Pathology, Dalian Medical University, Dalian 116044, China.
Yu
Y
Guo
Department of Pathology, Dalian Medical University, Dalian 116044, China.
Li
L
Wang
Department of Pathology, Dalian Medical University, Dalian 116044, China.
Shuting
S
Zhou
Department of Pathology, Dalian Medical University, Dalian 116044, China.
Boyi
B
Xin
Department of Pathology, Dalian Medical University, Dalian 116044, China.
Wei
W
Xuan
Department of Pathology, Dalian Medical University, Dalian 116044, China.
Jianwu
J
Tang
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D058851:GPI-Linked Proteins / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology*; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D000090204:Mesothelin; D051379:Mice; D015238:Sulfotransferases / Q000235:genetics* / Q000378:metabolism
D058851:GPI-Linked Proteins; C000715528:Msln protein, mouse; C486773:Sulf1 protein, mouse; D015238:Sulfotransferases; D000090204:Mesothelin
hepatocellular carcinoma; lymph node metastasis; mesothelin; migration and invasion; sulfatase-1