Secreted Gaussia Luciferase as a Biomarker for Monitoring Tumor Progression and Treatment Response of Systemic Metastases
Year: 2009
Type: article
Abstract: BACKGROUND: Currently, only few techniques are available for quantifying systemic metastases in preclinical model. Thus techniques that can sensitively detect metastatic colonization and assess treatment response in real-time are urgently needed. To this end, we engineered tumor cells to express a naturally secreted Gaussia luciferase (Gluc), and investigated its use as a circulating biomarker for monitoring viable metastatic or primary tumor growth and their treatment responses. METHODOLOGY/PRINCIPAL FINDINGS: We first developed orthotopic primary and metastatic breast tumors with derivative of MDA-MB-231 cells expressing Gluc. We then correlated tumor burden with Gluc activity in the blood and urine along with bioluminescent imaging (BLI). Second, we utilized blood Gluc assay to monitor treatment response to lapatinib in an experimental model of systemic metastasis. We observed good correlation between the primary tumor volume and Gluc concentration in blood (R(2) = 0.84) and urine (R(2) = 0.55) in the breast tumor model. The correlation deviated as a primary tumor grew due to a reduction in viable tumor fraction. This was also supported by our mathematical models for tumor growth to compare the total and viable tumor burden in our model. In the experimental metastasis model, we found numerous brain metastases as well as systemic metastases including bone and lungs. Importantly, blood Gluc assay revealed early growth of metastatic tumors before BLI could visualize their presence. Using secreted Gluc, we localized systemic metastases by BLI and quantitatively monitored the total viable metastatic tumor burden by blood Gluc assay during the course of treatment with lapatinib, a dual tyrosine kinase inhibitor of EGFR and HER2. CONCLUSION/SIGNIFICANCE: We demonstrated secreted Gluc assay accurately reflects the amount of viable cancer cells in primary and metastatic tumors. Blood Gluc activity not only tracks metastatic tumor progression but also serves as a longitudinal biomarker for tumor response to treatments.
Source: PLoS ONE
Authors: Euiheon Chung, Hiroshi Yamashita, Patrick Au, Bakhos A. Tannous, Dai Fukumura, Rakesh K. Jain
Institutions: Harvard University, Massachusetts General Hospital
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,382
Awards: G1049334674, Role of BMDCs in Solid Tumor Growth and Relapse, G152233900, G17656406, Training Program in Integrative Pathophysiology of Solid Tumors, G2161317883, G2247324011, Center for Molecular Imaging Research at MGH/HMS, Glioblastoma stem cells therapy, G3216449069, Integrative Biology of Tumor Metastasis, Nitric Oxide in Tumor Angiogenesis, Microcirculation and Radiation Therapy, BIOLOGY OF TUMOR ANGIOGENESIS, INVASION AND METASTASIS, G5230703566, Imaging and therapy of tumors using biotinylated cell surface docking sites, Integrative Pathophysiology of Solid Tumors, Probing Tumor Microenvironment Using Nanotechnology, G635729992, G901775365, G957989938, G976294263
OpenAlex ID: W2083797848