Downregulation of discoidin domain receptor 2 decreases tumor growth of hepatocellular carcinoma.

Abstract

PURPOSE:

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: Joong-Won Park, Yeon-Su Lee, Jin Sook Kim, Sook-Kyung Lee, Bo Hyun Kim, Jung Ahn Lee, Nam Oak Lee, Seong Hoon Kim, Eun Kyung Hong
• Journal: Journal of cancer research and clinical oncology (J Cancer Res Clin Oncol) Vol. 141 Issue 11 Pg. 1973-83 (Nov 2015) ISSN: 1432-1335 [Electronic] Germany
• PMID: 25842034 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Small Interfering
• Receptors, Mitogen
• Discoidin Domain Receptors
• Receptor Protein-Tyrosine Kinases

Topics

• 3T3 Cells
• Animals
• Apoptosis (genetics)
• Carcinoma, Hepatocellular (genetics, pathology)
• Cell Adhesion (genetics)
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• Discoidin Domain Receptors
• Disease Progression
• HeLa Cells
• Humans
• Liver Neoplasms (genetics, pathology)
• MCF-7 Cells
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Transplantation
• RNA Interference
• RNA, Small Interfering (genetics)
• Receptor Protein-Tyrosine Kinases (biosynthesis, genetics)
• Receptors, Mitogen (biosynthesis, genetics)
• Transfection
• Tumor Burden (genetics)