RRC ID 65836
Author Honda H, Takamura M, Yamagiwa S, Genda T, Horigome R, Kimura N, Setsu T, Tominaga K, Kamimura H, Matsuda Y, Wakai T, Aoyagi Y, Terai S.
Title Overexpression of a disintegrin and metalloproteinase 21 is associated with motility, metastasis, and poor prognosis in hepatocellular carcinoma.
Journal Sci Rep
Abstract Cell motility plays an important role in intrahepatic metastasis of hepatocellular carcinoma (HCC), and predicts poor prognosis in patients. The present study investigated the role of a disintegrin and metalloproteinases (ADAMs) in HCC, since these proteins are known to be associated with cell motility. We confirmed the expression of 12 ADAMs with putative metalloproteinase activity in HCC cells, and established a KYN-2 HCC cell line stably expressing short interfering RNA against ADAM21 to investigate the effect of ADAM21 deficiency on HCC cell motility and metastasis in vitro and in vivo. We also examined ADAM21 expression in a cohort of 119 HCC patients by immunohistochemistry. ADAM21 was overexpressed in KYN-2 cells, and its knockdown reduced invasion, migration, proliferation, and metastasis relative to controls. In clinical specimens, ADAM21 positivity was associated with vascular invasion, large tumor size, high histological grade, and lower overall and recurrence-free survival as compared to cases that were negative for ADAM21 expression. A multivariate analysis revealed that ADAM21 positivity was an independent risk factor for overall (P = 0.003) and recurrence-free (P = 0.001) survival. These results suggest that ADAM21 plays a role in HCC metastasis and can serve as a prognostic marker for disease progression.
Volume 7(1)
Pages 15485
Published 2017-11-14
DOI 10.1038/s41598-017-15800-z
PII 10.1038/s41598-017-15800-z
PMID 29138461
PMC PMC5686078
MeSH ADAM Proteins / genetics ADAM Proteins / metabolism* Adult Aged Aged, 80 and over Animals Biomarkers, Tumor / metabolism* Carcinoma, Hepatocellular / mortality Carcinoma, Hepatocellular / pathology* Carcinoma, Hepatocellular / surgery Cell Line, Tumor Cell Movement Disease-Free Survival Female Follow-Up Studies Gene Knockdown Techniques Hepatectomy Humans Liver / pathology Liver Neoplasms / mortality Liver Neoplasms / pathology* Liver Neoplasms / surgery Male Membrane Proteins / genetics Membrane Proteins / metabolism* Mice Mice, SCID Middle Aged Prognosis RNA, Small Interfering / metabolism Xenograft Model Antitumor Assays
IF 3.998
Human and Animal Cells Hep G2