Abstract
Only a few techniques are currently available for quantifying systemic metastases in preclinical models. Cancer cell expression of naturally secreted Gaussia luciferase (Gluc) provides a useful circulating biomarker that enables the monitoring of metastatic tumor burden and of treatment response from minimal drops of blood. This blood-based Gluc assay exhibits several distinct advantages: (1) It is highly sensitive in quantifying metastatic tumor growth, particularly when compared to whole-body bioluminescence imaging (BLI) alone; (2) It is quantitative by nature and reflects viable tumor burden in a minimally invasive manner; (3) Through longitudinal collection of blood samples, treatment response can be monitored in real-time; and (4) Gluc bioluminescence provides a means to localize and assess metastatic colonization using BLI. By elucidating the progression of systemic metastases and therapeutic response in animal models, the blood-based Gluc assay is emerging as a valuable quantitative tool for novel drug development.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsSpringer Nature is developing a new tool to find and evaluate Protocols. Learn more
References
Contag CH (2007) In vivo pathology: seeing with molecular specificity and cellular resolution in the living body. Annu Rev Pathol 2:277–305
Chung E, Yamashita H, Au P et al (2009) Secreted Gaussia luciferase as a biomarker for monitoring tumor progression and treatment response of systemic metastases. PLoS ONE 4:e8316
Wurdinger T, Badr C, Pike L et al (2008) A secreted luciferase for ex vivo monitoring of in vivo processes. Nat Methods 5:171–173
Hewett JW, Tannous B, Niland BP et al (2007) Mutant torsinA interferes with protein processing through the secretory pathway in DYT1 dystonia cells. Proc Natl Acad Sci U S A 104:7271–7276
Badr CE, Hewett JW, Breakefield XO, Tannous BA (2007) A highly sensitive assay for monitoring the secretory pathway and ER stress. PLoS ONE 2:e571
Bao R, Connolly DC, Murphy M et al (2002) Activation of cancer-specific gene expression by the survivin promoter. J Natl Cancer Inst 94:522–528
Bao R, Selvakumaran M, Hamilton TC (2000) Use of a surrogate marker (human secreted alkaline phosphatase) to monitor in vivo tumor growth and anticancer drug efficacy in ovarian cancer xenografts. Gynecol Oncol 78:373–379
Hiramatsu N, Kasai A, Hayakawa K et al (2006) Secreted protein-based reporter systems for monitoring inflammatory events: critical interference by endoplasmic reticulum stress. J Immunol Methods 315:202–207
Meng Y, Kasai A, Hiramatsu N et al (2005) Continuous, noninvasive monitoring of local microscopic inflammation using a genetically engineered cell-based biosensor. Lab Invest 85:1429–1439
Kim HJ, Kim YH, Lee DS et al (2008) In vivo imaging of functional targeting of miR-221 in papillary thyroid carcinoma. J Nucl Med 49:1686–1693
Kodack DP, Chung E, Yamashita H et al (2012) Combined targeting of HER2 and VEGFR2 for effective treatment of HER2-amplified breast cancer brain metastases. Proc Natl Acad Sci U S A 109:E3119–E3127
Tannous BA (2009) Gaussia luciferase reporter assay for monitoring biological processes in culture and in vivo. Nat Protoc 4:582–591
Badr CE, Tannous BA (2011) Bioluminescence imaging: progress and applications. Trends Biotechnol 29:624–633
Tannous BA, Kim DE, Fernandez JL et al (2005) Codon-optimized Gaussia luciferase cDNA for mammalian gene expression in culture and in vivo. Mol Ther 11:435–443
Korpal M, Yan J, Lu X et al (2009) Imaging transforming growth factor-beta signaling dynamics and therapeutic response in breast cancer bone metastasis. Nat Med 15:960–966
Bhaumik S, Gambhir SS (2002) Optical imaging of Renilla luciferase reporter gene expression in living mice. Proc Natl Acad Sci U S A 99:377–382
Palmieri D, Bronder JL, Herring JM et al (2007) Her-2 overexpression increases the metastatic outgrowth of breast cancer cells in the brain. Cancer Res 67:4190–4198
Acknowledgements
The authors are grateful for the support of the Steele Laboratory for Tumor Biology (PI: Rakesh K. Jain) and Prof. Bakhos A. Tannous at the Massachusetts General Hospital. This work was supported by grants from the Institute of Medical System Engineering and the Bio Imaging Research Center at Gwangju Institute of Science and Technology (GIST); Basic Research Projects in High-tech Industrial Technology at GIST; the Institute of Medical System Engineering at GIST; the Bio & Medical Technology Development Program and Basic Science Program through the National Research Foundation of Korea Grants 2011-0019633 and 2012R1A1A1012853, and the Tosteson postdoctoral fellowship at the Massachusetts General Hospital (to E.C.)
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer Science+Business Media New York
About this protocol
Cite this protocol
Yamashita, H., Nguyen, D.T., Chung, E. (2014). Blood-Based Assay with Secreted Gaussia Luciferase to Monitor Tumor Metastasis. In: Badr, C. (eds) Bioluminescent Imaging. Methods in Molecular Biology, vol 1098. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-718-1_12
Download citation
DOI: https://doi.org/10.1007/978-1-62703-718-1_12
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-62703-717-4
Online ISBN: 978-1-62703-718-1
eBook Packages: Springer Protocols