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  • Multimodality imaging of TGFβ signaling in breast cancer metastases

    Author(s)
    Serganova, Inna
    Moroz, Ekaterina
    Vider, Jelena
    Gogiberidze, George
    Moroz, Maxim
    Pillarsetty, Nagavarakishore
    Doubrovin, Michael
    Minn, Andy
    Thaler, Howard T
    Massague, Joan
    Gelovani, Juri
    Blasberg, Ronald
    Griffith University Author(s)
    Vider, Jelena
    Year published
    2009
    Metadata
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    Abstract
    The skeleton is a preferred site for breast cancer metastasis. We have developed a multimodality imaging approach to monitor the transforming growth factor beta (TGFbeta) signaling pathway in bone metastases, sequentially over time in the same animal. As model systems, two MDA-MB-231 breast cancer cells lines with different metastatic tropisms, SCP2 and SCP3, were transduced with constitutive and TGFbeta-inducible reporter genes and were tested in vitro and in living animals. The sites and expansion of metastases were visualized by bioluminescence imaging using a constitutive firefly luciferase reporter, while TGFbeta signaling ...
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    The skeleton is a preferred site for breast cancer metastasis. We have developed a multimodality imaging approach to monitor the transforming growth factor beta (TGFbeta) signaling pathway in bone metastases, sequentially over time in the same animal. As model systems, two MDA-MB-231 breast cancer cells lines with different metastatic tropisms, SCP2 and SCP3, were transduced with constitutive and TGFbeta-inducible reporter genes and were tested in vitro and in living animals. The sites and expansion of metastases were visualized by bioluminescence imaging using a constitutive firefly luciferase reporter, while TGFbeta signaling in metastases was monitored by microPET imaging of HSV1-TK/GFP expression with [(18)F]FEAU and by a more sensitive and cost-effective bioluminescence reporter, based on nonsecreted Gaussia luciferase. Concurrent and sequential imaging of metastases in the same animals provided insight into the location and progression of metastases, and the timing and course of TGFbeta signaling. The anticipated and newly observed differences in the imaging of tumors from two related cell lines have demonstrated that TGFbeta signal transduction pathway activity can be noninvasively imaged with high sensitivity and reproducibility, thereby providing the opportunity for an assessment of novel treatments that target TGFbeta signaling.
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    Journal Title
    The FASEB Journal
    Volume
    23
    Issue
    8
    DOI
    https://doi.org/10.1096/fj.08-126920
    Copyright Statement
    Self-archiving of the author-manuscript version is not yet supported by this journal. Please refer to the journal link for access to the definitive, published version or contact the author for more information.
    Subject
    Biochemistry and cell biology
    Zoology
    Cancer cell biology
    Medical physiology
    Publication URI
    http://hdl.handle.net/10072/44692
    Collection
    • Journal articles

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