secreted gaussia luciferase as a biomarker for monitoring tumor progression and treatment response of systemic metastases分泌gaussia荧光素酶作为一种生物标志物监测系统性转移的肿瘤进展和治疗反应.pdfVIP

Secreted Gaussia Luciferase as a Biomarker for Monitoring Tumor Progression and Treatment Response of Systemic Metastases 1. 1. 1 2,3 1 Euiheon Chung , Hiroshi Yamashita , Patrick Au , Bakhos A. Tannous *, Dai Fukumura *, Rakesh K. Jain1* 1 Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America, 2 Molecular Neurogenetics Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America, 3 Department of Radiology, Center for Molecular Imaging Research, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America 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