title: Single cell molecular recognition of migrating and invading tumor cells using a targeted fluorescent probe to receptor PTPmu.
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.
authors.affiliation: Department of Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, OH, USA. susann.brady-kalnay@case.edu
authors.forename: Susan M
authors.initials: SM
authors.lastname: Burden-Gulley
authors.forename: Mohammed Q
authors.initials: MQ
authors.lastname: Qutaish
authors.forename: Kristin E
authors.initials: KE
authors.lastname: Sullivant
authors.forename: Mingqian
authors.initials: M
authors.lastname: Tan
authors.forename: Sonya E L
authors.initials: SE
authors.lastname: Craig
authors.forename: James P
authors.initials: JP
authors.lastname: Basilion
authors.forename: Zheng-Rong
authors.initials: ZR
authors.lastname: Lu
authors.forename: David L
authors.initials: DL
authors.lastname: Wilson
authors.forename: Susann M
authors.initials: SM
authors.lastname: Brady-Kalnay
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier; D001932:Brain Neoplasms / Q000201:enzymology / Q000473:pathology*; D002465:Cell Movement; D005110:Extracellular Space / Q000378:metabolism; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D005909:Glioblastoma / Q000201:enzymology / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D025202:Molecular Diagnostic Techniques; D015335:Molecular Probes; D010446:Peptide Fragments / Q000378:metabolism*; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D005456:Fluorescent Dyes; D015335:Molecular Probes; D010446:Peptide Fragments; C516859:PTPRM protein, human; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2