The KISS1 Receptor as an In Vivo Microenvironment Imaging Biomarker of Multiple Myeloma Bone Disease

• Published in: PloS one 2016-05, Vol.11 (5), p.e0155087-e0155087
• Main Authors: Dotterweich, Julia, Tower, Robert J, Brandl, Andreas, Müller, Marc, Hofbauer, Lorenz C, Beilhack, Andreas, Ebert, Regina, Glüer, Claus C, Tiwari, Sanjay, Schütze, Norbert, Jakob, Franz
• Format: Article
• Language: English
• Subjects: Aberration; Animals; Biocompatibility; Biological markers; Biology and Life Sciences; Biomarkers; Biomarkers, Tumor - metabolism; Biomedical materials; Bone cancer; Bone diseases; Bone imaging; Bone lesions; Bone marrow; Bone turnover; Cancer; Care and treatment; Cell culture; Cell proliferation; Cells, Cultured; Coculture Techniques; Complications and side effects; Crosstalk; Diagnostic imaging; Diagnostic systems; Endocrinology; Fluorescence; Fluorescent indicators; G protein-coupled receptors; Gene expression; Hematological diseases; Hematology; Homeostasis; Hospitals; Humans; Immunoglobulins; In vivo methods and tests; Interdisciplinary aspects; Internal medicine; Joint surgery; Kinases; Kiss1 protein; Laboratories; Lesions; Light chains; Medical imaging; Medicine; Medicine and Health Sciences; Mesenchymal Stem Cells - metabolism; Mesenchyme; Metabolism; Metastasis; Mice; Microscopy; Multiple myeloma; Multiple Myeloma - metabolism; Multiple Myeloma - pathology; Osteolysis; Osteoprogenitor cells; Pharmaceutical sciences; Physical Sciences; Physiology; Plasma cells; Prognosis; Proteins; Receptors, G-Protein-Coupled - metabolism; Receptors, Kisspeptin-1; Research and Analysis Methods; Rodents; Stem cell transplantation; Stem cells; Target recognition; Tumor cells; Tumor Microenvironment; Urine
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0155087

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.