Please use this identifier to cite or link to this item: https://doi.org/10.3389/fbioe.2020.00412
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dc.titlepHLuc, a Ratiometric Luminescent Reporter for in vivo Monitoring of Tumor Acidosis
dc.contributor.authorOng, Tiffany T
dc.contributor.authorAng, Zhiwei
dc.contributor.authorVerma, Riva
dc.contributor.authorKoean, Ricky
dc.contributor.authorTam, John Kit Chung
dc.contributor.authorDing, Jeak Ling
dc.date.accessioned2021-07-06T12:18:30Z
dc.date.available2021-07-06T12:18:30Z
dc.date.issued2020-05-08
dc.identifier.citationOng, Tiffany T, Ang, Zhiwei, Verma, Riva, Koean, Ricky, Tam, John Kit Chung, Ding, Jeak Ling (2020-05-08). pHLuc, a Ratiometric Luminescent Reporter for in vivo Monitoring of Tumor Acidosis. FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY 8. ScholarBank@NUS Repository. https://doi.org/10.3389/fbioe.2020.00412
dc.identifier.issn22964185
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/193726
dc.description.abstractEven under normoxia, cancer cells exhibit increased glucose uptake and glycolysis, an occurrence known as the Warburg effect. This altered metabolism results in increased lactic acid production, leading to extracellular acidosis and contributing to metastasis and chemoresistance. Current pH imaging methods are invasive, costly, or require long acquisition times, and may not be suitable for high-throughput pre-clinical small animal studies. Here, we present a ratiometric pH-sensitive bioluminescence reporter called pHLuc for in vivo monitoring of tumor acidosis. pHLuc consists of a pH-sensitive GFP (superecliptic pHluorin or SEP), a pH-stable OFP (Antares), and Nanoluc luciferase. The resulting reporter produces a pH-responsive green 510nm emission (from SEP) and a pH-insensitive red-orange 580nm emission (from Antares). The ratiometric readout (R580/510) is indicative of changes in extracellular pH (pHe). In vivo proof-of-concept experiments with NSG mice model bearing human synovial sarcoma SW982 xenografts that stably express the pHLuc reporter suggest that the level of acidosis varies across the tumor. Altogether, we demonstrate the diagnostic value of pHLuc as a bioluminescent reporter for pH variations across the tumor microenvironment. The pHLuc reporter plasmids constructed in this work are available from Addgene.
dc.language.isoen
dc.publisherFRONTIERS MEDIA SA
dc.sourceElements
dc.subjectScience & Technology
dc.subjectLife Sciences & Biomedicine
dc.subjectBiotechnology & Applied Microbiology
dc.subjectMultidisciplinary Sciences
dc.subjectScience & Technology - Other Topics
dc.subjectpH-sensitive ratiometric luminescent reporter
dc.subjectSuperecliptic pHluorin (SEP)
dc.subjectNanoluc
dc.subjecttumor microenvironment
dc.subjectacidosis
dc.subjectbioluminescence resonance energy transfer
dc.subjectPROTEIN-PROTEIN INTERACTIONS
dc.subjectIMAGING PH
dc.subjectCANCER
dc.subjectMRI
dc.typeArticle
dc.date.updated2021-07-06T07:42:47Z
dc.contributor.departmentBIOLOGICAL SCIENCES
dc.contributor.departmentSURGERY
dc.description.doi10.3389/fbioe.2020.00412
dc.description.sourcetitleFRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
dc.description.volume8
dc.published.statePublished
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