title: Downregulation of discoidin domain receptor 2 decreases tumor growth of hepatocellular carcinoma.
abstract: OBJECTIVE
  Discoidin domain receptors (DDRs) have been identified as tyrosine kinase receptors for collagen, and the overexpression of DDR1 was correlated with hepatocellular carcinoma (HCC) progression in vitro. Little is known about DDR2 on HCC cells, and we investigated the expression and function of DDR2 in human HCC cells.
  
  
  METHODS
  Expression of DDR2 in human HCC cell lines and patient HCC tissues was observed. The suppression of DDR2 by siRNA against DDR2 was performed in vitro and in vivo study.
  
  
  RESULTS
  All of HCC cell lines expressed DDR2 mRNA, and all HCC tissues from the ten patients with HCC demonstrated DDR2 mRNA expression. Transfection of DDR2 siRNA significantly inhibits cell growth compared to cells with nontarget siRNA transfection in vitro (P < 0.001). In SNU182, Hep3B, and HeLa cell xenograft models, there was a significant difference in average tumor volumes after 12 days of the DDR2 siRNA injection (P < 0.05) in SNU182 xenograft mice. DDR2 siRNA injection decreased the mean tumor volume by 65.6 % compared to that of the control. The apoptosis analysis demonstrated that DDR2 siRNA treatment significantly increased apoptotic cells (P < 0.01). Cell migration (P < 0.05) and cell invasion (P < 0.01) were significantly decreased by DDR2 siRNA treatment.
  
  
  CONCLUSIONS
  The inhibition of DDR2 by RNA interference suppressed in vivo and in vitro growth of human HCC cells. Our results may support that the use of DDR2 as a novel target of HCC treatment through control of tumor apoptosis, migration, and invasion.
authors.affiliation: Liver and Pancreatobiliary Cancer Research Branch, National Cancer Center, Goyang, South Korea. jwpark@ncc.re.kr.|Center for Liver Cancer, National Cancer Center, 323 Ilsan-ro, Ilsan dong-gu, Goyang, Gyeonggi, 411-769, South Korea. jwpark@ncc.re.kr.
authors.forename: Joong-Won
authors.initials: JW
authors.lastname: Park
authors.affiliation: Functional Genomics Branch, National Cancer Center, Goyang, South Korea. yslee2@ncc.re.kr.
authors.forename: Yeon-Su
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Liver and Pancreatobiliary Cancer Research Branch, National Cancer Center, Goyang, South Korea. 73058@ncc.re.kr.
authors.forename: Jin Sook
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Liver and Pancreatobiliary Cancer Research Branch, National Cancer Center, Goyang, South Korea. 73246@ncc.re.kr.
authors.forename: Sook-Kyung
authors.initials: SK
authors.lastname: Lee
authors.affiliation: Center for Liver Cancer, National Cancer Center, 323 Ilsan-ro, Ilsan dong-gu, Goyang, Gyeonggi, 411-769, South Korea. bohkim@ncc.re.kr.
authors.forename: Bo Hyun
authors.initials: BH
authors.lastname: Kim
authors.affiliation: Liver and Pancreatobiliary Cancer Research Branch, National Cancer Center, Goyang, South Korea. chingal@hanmail.net.
authors.forename: Jung Ahn
authors.initials: JA
authors.lastname: Lee
authors.affiliation: Liver and Pancreatobiliary Cancer Research Branch, National Cancer Center, Goyang, South Korea. leeno1752@naver.com.
authors.forename: Nam Oak
authors.initials: NO
authors.lastname: Lee
authors.affiliation: Liver and Pancreatobiliary Cancer Research Branch, National Cancer Center, Goyang, South Korea. kshlj@ncc.re.kr.|Center for Liver Cancer, National Cancer Center, 323 Ilsan-ro, Ilsan dong-gu, Goyang, Gyeonggi, 411-769, South Korea. kshlj@ncc.re.kr.
authors.forename: Seong Hoon
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Liver and Pancreatobiliary Cancer Research Branch, National Cancer Center, Goyang, South Korea. hongek@ncc.re.kr.|Center for Liver Cancer, National Cancer Center, 323 Ilsan-ro, Ilsan dong-gu, Goyang, Gyeonggi, 411-769, South Korea. hongek@ncc.re.kr.
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Hong
mesh_terms: D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology*; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D000070818:Discoidin Domain Receptors; D018450:Disease Progression; D006367:HeLa Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology*; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics*; D011975:Receptors, Mitogen / Q000096:biosynthesis / Q000235:genetics*; D014162:Transfection; D047368:Tumor Burden / Q000235:genetics
chemical_list: D034741:RNA, Small Interfering; D011975:Receptors, Mitogen; D000070818:Discoidin Domain Receptors; D020794:Receptor Protein-Tyrosine Kinases
keywords: DDR2; Growth inhibition; Hepatocellular carcinoma
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