Single cell molecular recognition of migrating and invading tumor cells using a targeted fluorescent probe to receptor PTPmu

Authors

  • Susan M. Burden-Gulley,

    Corresponding author
    1. Department of Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, OH
    • Department of Molecular Biology and Microbiology, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-4960, USA
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    • Tel.: +216-368-0330, Fax: +216-368-3055

    • S.M.B.-G. and M.Q.Q. contributed equally to this work

    • S.M.B.-G. and M.Q.Q. contributed equally to this work

  • Mohammed Q. Qutaish,

    1. Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH
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    • S.M.B.-G. and M.Q.Q. contributed equally to this work

  • Kristin E. Sullivant,

    1. Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH
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  • Mingqian Tan,

    1. Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH
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  • Sonya E.L. Craig,

    1. Department of Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, OH
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  • James P. Basilion,

    1. Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH
    2. NFCR Center for Molecular Imaging at Case Western Reserve University and Department of Radiology, Case Western Reserve University, Cleveland, OH
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  • Zheng-Rong Lu,

    1. Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH
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  • David L. Wilson,

    1. Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH
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  • Susann M. Brady-Kalnay

    1. Department of Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, OH
    2. Department of Neuroscience, Case Western Reserve University, Cleveland, OH
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  • Conflict of interest: Dr. Wilson has a financial interest in BioInVision Inc., which is commercializing cryo-imaging.

Abstract

Detection of an extracellular cleaved fragment of a cell–cell adhesion molecule represents a new paradigm in molecular recognition and imaging of tumors. We previously demonstrated that probes that recognize the cleaved extracellular domain of receptor protein tyrosine phosphatase mu (PTPmu) label human glioblastoma brain tumor sections and the main tumor mass of intracranial xenograft gliomas. In this article, we examine whether one of these probes, SBK2, can label dispersed glioma cells that are no longer connected to the main tumor mass. Live mice with highly dispersive glioma tumors were injected intravenously with the fluorescent PTPmu probe to test the ability of the probe to label the dispersive glioma cells in vivo. Analysis was performed using a unique three-dimensional (3D) cryo-imaging technique to reveal highly migratory and invasive glioma cell dispersal within the brain and the extent of colabeling by the PTPmu probe. The PTPmu probe labeled the main tumor site and dispersed cells up to 3.5 mm away. The cryo-images of tumors labeled with the PTPmu probe provide a novel, high-resolution view of molecular tumor recognition, with excellent 3D detail regarding the pathways of tumor cell migration. Our data demonstrate that the PTPmu probe recognizes distant tumor cells even in parts of the brain where the blood–brain barrier is likely intact. The PTPmu probe has potential translational significance for recognizing tumor cells to facilitate molecular imaging, a more complete tumor resection and to serve as a molecular targeting agent to deliver chemotherapeutics to the main tumor mass and distant dispersive tumor cells.

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