title: Targeting canine bladder transitional cell carcinoma with a human bladder cancer-specific ligand.
abstract: OBJECTIVE
  To determine if a human bladder cancer-specific peptide named PLZ4 can target canine bladder cancer cells.
  
  
  METHODS
  The binding of PLZ4 to five established canine invasive transitional cell carcinoma (TCC) cell lines and to normal canine bladder urothelial cells was determined using the whole cell binding assay and an affinitofluorescence assay. The WST-8 assay was performed to determine whether PLZ4 affected cell viability. In vivo tumor-specific homing/targeting property and biodistribution of PLZ4 was performed in a mouse xenograft model via tail vein injection and was confirmed with ex vivo imaging.
  
  
  RESULTS
  PLZ4 exhibited high affinity and specific dose-dependent binding to canine bladder TCC cell lines, but not to normal canine urothelial cells. No significant changes in cell viability or proliferation were observed upon incubation with PLZ4. The in vivo and ex vivo optical imaging study showed that, when linked with the near-infrared fluorescent dye Cy5.5, PLZ4 substantially accumulated at the canine bladder cancer foci in the mouse xenograft model as compared to the control.
  
  
  CONCLUSIONS
  PLZ4 can specifically bind to canine bladder cancer cells. This suggests that the preclinical studies of PLZ4 as a potential diagnostic and therapeutic agent can be performed in dogs with naturally occurring bladder cancer, and that PLZ4 can possibly be developed in the management of canine bladder cancer.
authors.affiliation: Division of Hematology and oncology, Department of Internal Medicine, University of California-Davis Cancer Center, Sacramento, CA 95817, USA.
authors.forename: Tzu-yin
authors.initials: TY
authors.lastname: Lin
authors.forename: Hongyong
authors.initials: H
authors.lastname: Zhang
authors.forename: Sisi
authors.initials: S
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Xie
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.forename: Carlos O
authors.initials: CO
authors.lastname: Rodriguez
authors.forename: Ralph
authors.initials: R
authors.lastname: de Vere White
authors.forename: Chong-xian
authors.initials: CX
authors.lastname: Pan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy / Q000473:pathology / Q000662:veterinary*; D002470:Cell Survival / Q000187:drug effects; D004283:Dog Diseases / Q000188:drug therapy* / Q000473:pathology; D004285:Dogs; D006801:Humans; D008024:Ligands; D051379:Mice; D009368:Neoplasm Transplantation; D009842:Oligopeptides / Q000494:pharmacology* / Q000627:therapeutic use; D010456:Peptides, Cyclic / Q000627:therapeutic use*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000662:veterinary*
chemical_list: D000970:Antineoplastic Agents; D008024:Ligands; D009842:Oligopeptides; C558117:PLZ4 peptide; D010456:Peptides, Cyclic