These three authors made an equal contribution towards the conduct and reporting of this study.
Novel anti-tumor mechanism of galanin receptor type 2 in head and neck squamous cell carcinoma cells
Article first published online: 1 DEC 2013
© 2013 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Volume 105, Issue 1, pages 72–80, January 2014
How to Cite
Cancer Sci 105 (2014) 72–80
- Issue published online: 24 JAN 2014
- Article first published online: 1 DEC 2013
- Accepted manuscript online: 29 OCT 2013 11:53PM EST
- Manuscript Accepted: 27 OCT 2013
- Manuscript Revised: 23 OCT 2013
- Manuscript Received: 25 JUN 2013
- Ministry of Education, Culture, Sports, Science, and Technology of Japan. Grant Numbers: 22591916, 23592539
- Adeno-associated virus vector;
- extracellular signal-regulated kinases 1/2;
- galanin receptor;
- head and neck squamous cell carcinoma
Galanin and its receptors, GALR1 and GALR2, are known tumor suppressors and potential therapeutic targets in head and neck squamous cell carcinoma (HNSCC). Previously, we demonstrated that, in GALR1-expressing HNSCC cells, the addition of galanin suppressed tumor proliferation via upregulation of ERK1/2 and cyclin-dependent kinase inhibitors, whereas, in GALR2-expressing cells, the addition of galanin not only suppressed proliferation, but also induced apoptosis. In this study, we first transduced HEp-2 and KB cell lines using a recombinant adeno-associated virus (rAAV)-green fluorescent protein (GFP) vector and confirmed a high GFP expression rate (>90%) in both cell lines at the standard vector dose. Next, we demonstrated that GALR2 expression in the presence of galanin suppressed cell viability to 40–60% after 72 h in both cell lines. Additionally, the annexin V-positive rate and sub-G0/G1 phase population were significantly elevated in HEp-2 cells (mock vs GALR2: 12.3 vs 25.0% (P < 0.01) and 9.1 vs 32.0% (P < 0.05), respectively) after 48 h. These changes were also observed in KB cells, although to a lesser extent. Furthermore, in HEp-2 cells, GALR2-mediated apoptosis was caspase-independent, involving downregulation of ERK1/2, followed by induction of the pro-apoptotic Bcl-2 protein, Bim. These results illustrate that transient GALR2 expression in the presence of galanin induces apoptosis via diverse pathways and serves as a platform for suicide gene therapy against HNSCC.