Research Papers: General

Effect of antiangiogenic therapy on luciferase activity in a cytomegalovirus- or HSP70-promoter-transfected M21 tumor model

[+] Author Affiliations
Walter Hundt

Stanford School of Medicine, Lucas MRS Research Center, Department of Radiology, Stanford, California

Philipps University Marburg, Department of Radiology, Marburg, Germany

Christian Schink

Philipps University Marburg, Department of Clinical Cytobiology and Cytopathology, Marburg, Germany

Silke Steinbach

Philipps University Marburg, Department of Otolaryngology Head and Neck Surgery, Marburg, Germany

Caitlin E. O’Connell-Rodwell

Stanford School of Medicine, Department of Pediatrics, Microbiology & Immunology and Radiology, Stanford, California 94305

Andreas Kiessling, Mykhaylo Burbelko

Philipps University Marburg, Department of Radiology, Marburg, Germany

Damiano Librizzi

Philipps University Marburg, Department of Nuclear Medicine, Marburg, Germany

Samira Guccione

Stanford School of Medicine, Lucas MRS Research Center, Department of Radiology, Stanford, California

J. Biomed. Opt. 17(6), 065001 (Jun 05, 2012). doi:10.1117/1.JBO.17.6.065001
History: Received February 23, 2012; Revised April 23, 2012; Accepted April 24, 2012
Text Size: A A A

Abstract.  We investigated the effect of targeted gene therapy on heat shock protein 70 expression (Hsp70) and protein production (HSP70) in a melanoma tumor model (M21; M21-L). M21 and M21-L cells transfected with a plasmid containing the Hsp70 (Hspa1b) or the cytomegalovirus (CMV) promoter and the luciferase reporter gene were injected into mice; the resulting tumors grew to a size of 650mm3. Mice (five per group) were intravenously treated with an Arg-Gly-Asp peptide-nanoparticle/Raf-1 kinase inhibitor protein complex [RGD-NP/RAF(-)] or with a nanoparticle control. Bioluminescence imaging (IVIS®, Xenogen, USA) was performed at 12, 24, 48, and 72 h after the treatment cycle. Western blot analysis of HSP70 protein was performed to monitor protein expression. The size of the treated M21 tumors remained fairly constant (647.8±103.4mm2 at the beginning versus 704.8±94.4mm3 at the end of the experiment). The size of the M21-L tumors increased, similar to the untreated control tumors. Bioluminescent imaging demonstrated that when transcription was controlled by the CMV promoter, luciferase activity decreased to 17.9%±4.3% of baseline values in the treated M21 tumors. When transcription was controlled by the Hsp70 promoter, the highest luciferase activity (4.5±0.7-fold increase over base-line values) was seen 24 h after injection in the M21 tumors; however, no luciferase activity was seen in the M21-L tumors. In accordance with bioluminescent imaging, western blot analysis showed a peak in HSP70 production at 24 h after the injection of the RGD-NP/RAF(-) complex in the M21 tumors; however, no HSP70 protein induction was seen in the M21-L tumors. Thus, targeted antiangiogenic therapy can induce Hsp70 expression and HSP70 protein in melanoma tumors.

Figures in this Article
© 2012 Society of Photo-Optical Instrumentation Engineers

Citation

Walter Hundt ; Christian Schink ; Silke Steinbach ; Caitlin E. O’Connell-Rodwell ; Andreas Kiessling, et al.
"Effect of antiangiogenic therapy on luciferase activity in a cytomegalovirus- or HSP70-promoter-transfected M21 tumor model", J. Biomed. Opt. 17(6), 065001 (Jun 05, 2012). ; http://dx.doi.org/10.1117/1.JBO.17.6.065001


Tables

Access This Article
Sign in or Create a personal account to Buy this article ($20 for members, $25 for non-members).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Related Book Chapters

Topic Collections

PubMed Articles
Advertisement
  • Don't have an account?
  • Subscribe to the SPIE Digital Library
  • Create a FREE account to sign up for Digital Library content alerts and gain access to institutional subscriptions remotely.
Access This Article
Sign in or Create a personal account to Buy this article ($20 for members, $25 for non-members).
Access This Proceeding
Sign in or Create a personal account to Buy this article ($15 for members, $18 for non-members).
Access This Chapter

Access to SPIE eBooks is limited to subscribing institutions and is not available as part of a personal subscription. Print or electronic versions of individual SPIE books may be purchased via SPIE.org.