title: Fluorescent LYVE-1 antibody to image dynamically lymphatic trafficking of cancer cells in vivo.
abstract: BACKGROUND
  The lymphatic system is a major route for cancer cell dissemination, and a potential target for antitumor therapy. Despite ongoing interest in this area of research, the real-time behavior of cancer cells trafficking in the lymphatic system is poorly understood due to lack of appropriate tools to image this process.
  
  
  METHODS
  We have used monoclonal-antibody and fluorescence technology to color-code lymphatic vessels and the cancer cells inside them in a living animal. Monoclonal anti-mouse LYVE-1 antibody was conjugated to a green fluorophore and delivered to the lymphatic system of a nude mouse, allowing imaging of mouse lymphatics. Tumor cells engineered to express red fluorescent protein were then imaged traveling within the labeled lymphatics in real time.
  
  
  RESULTS
  AlexaFluor-labeled monoclonal anti-mouse LYVE-1 created a durable signal with clear delineation of lymphatic architecture. The duration of fluorescent signal after conjugated LYVE-1 delivery was far superior to that of fluorescein isothiocyanate-dextran or control fluorophore-conjugated IgG. Tumor cells engineered to express red fluorescent protein delivered to the inguinal lymph node enabled real-time tracking of tumor cell movement within the green fluorescent-labeled lymphatic vessels.
  
  
  CONCLUSIONS
  This technology offers a powerful tool for the in vivo study of real-time trafficking of tumor cells within lymphatic vessels, for the deposition of the tumor cells in lymph nodes, as well as for screening of potential antitumor lymphatic therapies.
authors.affiliation: Department of Surgery, University of California, San Diego, California, USA.
authors.forename: Michele
authors.initials: M
authors.lastname: McElroy
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Hayashi
authors.forename: Barbara
authors.initials: B
authors.lastname: Garmy-Susini
authors.forename: Sharmeela
authors.initials: S
authors.lastname: Kaushal
authors.forename: Judith A
authors.initials: JA
authors.lastname: Varner
authors.forename: A R
authors.initials: AR
authors.lastname: Moossa
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
authors.forename: Michael
authors.initials: M
authors.lastname: Bouvet
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D003952:Diagnostic Imaging / Q000379:methods*; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D006023:Glycoproteins; D006801:Humans; D008164:Luminescent Proteins; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology*; D042601:Lymphatic Vessels / Q000276:immunology / Q000473:pathology*; D026901:Membrane Transport Proteins; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000276:immunology / Q000473:pathology; D009360:Neoplastic Cells, Circulating; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000473:pathology*; D012190:Retroviridae; D014161:Transduction, Genetic; D000097573:Red Fluorescent Protein
chemical_list: D006023:Glycoproteins; D008164:Luminescent Proteins; D026901:Membrane Transport Proteins; D000097573:Red Fluorescent Protein; C492273:LYVE1 protein, mouse