title: The KISS1 Receptor as an In Vivo Microenvironment Imaging Biomarker of Multiple Myeloma Bone Disease.
abstract: Multiple myeloma is one of the most common hematological diseases and is characterized by an aberrant proliferation of plasma cells within the bone marrow. As a result of crosstalk between cancer cells and the bone microenvironment, bone homeostasis is disrupted leading to osteolytic lesions and poor prognosis. Current diagnostic strategies for myeloma typically rely on detection of excess monoclonal immunoglobulins or light chains in the urine or serum. However, these strategies fail to localize the sites of malignancies. In this study we sought to identify novel biomarkers of myeloma bone disease which could target the malignant cells and/or the surrounding cells of the tumor microenvironment. From these studies, the KISS1 receptor (KISS1R), a G-protein-coupled receptor known to play a role in the regulation of endocrine functions, was identified as a target gene that was upregulated on mesenchymal stem cells (MSCs) and osteoprogenitor cells (OPCs) when co-cultured with myeloma cells. To determine the potential of this receptor as a biomarker, in vitro and in vivo studies were performed with the KISS1R ligand, kisspeptin, conjugated with a fluorescent dye. In vitro microscopy showed binding of fluorescently-labeled kisspeptin to both myeloma cells as well as MSCs under direct co-culture conditions. Next, conjugated kisspeptin was injected into immune-competent mice containing myeloma bone lesions. Tumor-burdened limbs showed increased peak fluorescence compared to contralateral controls. These data suggest the utility of the KISS1R as a novel biomarker for multiple myeloma, capable of targeting both tumor cells and host cells of the tumor microenvironment.
authors.affiliation: Orthopedic Center for Musculoskeletal Research, Orthopedic Department, University of Würzburg, Würzburg, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Dotterweich
authors.affiliation: Section Biomedical Imaging, MOIN CC, Department of Radiology and Neuroradiology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Tower
authors.affiliation: Interdisciplinary Center for Clinical Research Laboratory, Department of Internal Medicine II, University Hospital of Würzburg, Würzburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Brandl
authors.affiliation: Section Biomedical Imaging, MOIN CC, Department of Radiology and Neuroradiology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Müller
authors.affiliation: Department of Medicine III, Technische Universität Dresden Medical Center, Dresden, Germany.
authors.forename: Lorenz C
authors.initials: LC
authors.lastname: Hofbauer
authors.affiliation: Interdisciplinary Center for Clinical Research Laboratory, Department of Internal Medicine II, University Hospital of Würzburg, Würzburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Beilhack
authors.affiliation: Orthopedic Center for Musculoskeletal Research, Orthopedic Department, University of Würzburg, Würzburg, Germany.
authors.forename: Regina
authors.initials: R
authors.lastname: Ebert
authors.affiliation: Section Biomedical Imaging, MOIN CC, Department of Radiology and Neuroradiology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Claus C
authors.initials: CC
authors.lastname: Glüer
authors.affiliation: Section Biomedical Imaging, MOIN CC, Department of Radiology and Neuroradiology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Tiwari
authors.affiliation: Orthopedic Center for Musculoskeletal Research, Orthopedic Department, University of Würzburg, Würzburg, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Schütze
authors.affiliation: Orthopedic Center for Musculoskeletal Research, Orthopedic Department, University of Würzburg, Würzburg, Germany.
authors.forename: Franz
authors.initials: F
authors.lastname: Jakob
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002478:Cells, Cultured; D018920:Coculture Techniques; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D051379:Mice; D009101:Multiple Myeloma / Q000378:metabolism* / Q000473:pathology; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D000074502:Receptors, Kisspeptin-1; D059016:Tumor Microenvironment
chemical_list: D014408:Biomarkers, Tumor; C118688:KISS1R protein, human; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1