title: Development of a brain metastatic canine prostate cancer cell line.
abstract: BACKGROUND
  Prostate cancer in men has a high mortality and morbidity due to metastatic disease. The pathobiology of prostate cancer metastasis is not well understood and cell lines and animal models that recapitulate the complex nature of the disease are needed. Therefore, the goal of the study was to establish and characterize a new prostate cancer line derived from a dog with spontaneous prostate cancer.
  
  
  METHODS
  A new cell line (Leo) was derived from a dog with spontaneous prostate cancer. Immunohistochemistry and PCR were used to characterize the primary prostate cancer and xenografts in nude mice. Subcutaneous tumor growth and metastases in nude mice were evaluated by bioluminescent imaging, radiography and histopathology. In vitro chemosensitivity of Leo cells to therapeutic agents was measured.
  
  
  RESULTS
  Leo cells expressed the secretory epithelial cytokeratins (CK)8, 18, and ductal cell marker, CK7. The cell line grew in vitro (over 75 passages) and was tumorigenic in the subcutis of nude mice. Following intracardiac injection, Leo cells metastasized to the brain, spinal cord, bone, and adrenal gland. The incidence of metastases was greatest to the central nervous system (80%) with a lower incidence to bone (20%) and the adrenal glands (16%). In vitro chemosensitivity assays demonstrated that Leo cells were sensitive to Velcade and an HDAC-42 inhibitor with IC(50) concentrations of 1.9 nm and 0.95 µm, respectively.
  
  
  CONCLUSIONS
  The new prostate cancer cell line (Leo) will be a valuable model to investigate the mechanisms of the brain and bone metastases.
authors.affiliation: Department of Radiation Oncology, University of Alabama, Birmingham, AL, USA.
authors.forename: Nanda K
authors.initials: NK
authors.lastname: Thudi
authors.forename: Sherry T
authors.initials: ST
authors.lastname: Shu
authors.forename: Chelsea K
authors.initials: CK
authors.lastname: Martin
authors.forename: Lisa G
authors.initials: LG
authors.lastname: Lanigan
authors.forename: Murali V P
authors.initials: MV
authors.lastname: Nadella
authors.forename: Adrie
authors.initials: A
authors.lastname: Van Bokhoven
authors.forename: Jillian L
authors.initials: JL
authors.lastname: Werbeck
authors.forename: Jessica K
authors.initials: JK
authors.lastname: Simmons
authors.forename: Sridhar
authors.initials: S
authors.lastname: Murahari
authors.forename: William C
authors.initials: WC
authors.lastname: Kisseberth
authors.forename: Matthew
authors.initials: M
authors.lastname: Breen
authors.forename: Christina
authors.initials: C
authors.lastname: Williams
authors.forename: Ching-Shih
authors.initials: CS
authors.lastname: Chen
authors.forename: Laurie K
authors.initials: LK
authors.lastname: McCauley
authors.forename: Evan T
authors.initials: ET
authors.lastname: Keller
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Rosol
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000453:epidemiology / Q000556:secondary; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001859:Bone Neoplasms / Q000453:epidemiology / Q000556:secondary; D001897:Boronic Acids / Q000494:pharmacology; D000069286:Bortezomib; D001932:Brain Neoplasms / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology* / Q000556:secondary*; D015197:Carcinogenicity Tests; D002277:Carcinoma / Q000453:epidemiology / Q000378:metabolism / Q000473:pathology* / Q000556:secondary*; D002455:Cell Division; D045744:Cell Line, Tumor / Q000187:drug effects / Q000473:pathology; D004285:Dogs; D007150:Immunohistochemistry; D015994:Incidence; D007279:Injections, Subcutaneous; D053538:Keratin-18 / Q000378:metabolism; D053552:Keratin-7 / Q000378:metabolism; D053533:Keratin-8 / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009372:Neoplasms, Connective Tissue / Q000556:secondary; D044162:Parathyroid Hormone-Related Protein / Q000378:metabolism; D010654:Phenylbutyrates / Q000037:antagonists & inhibitors; D011471:Prostatic Neoplasms / Q000473:pathology*; D011719:Pyrazines / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013120:Spinal Cord Neoplasms / Q000453:epidemiology / Q000556:secondary; D040521:Subcutaneous Tissue; D014183:Transplantation, Heterologous
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; C524513:HDAC-42; D053538:Keratin-18; D053552:Keratin-7; D053533:Keratin-8; D044162:Parathyroid Hormone-Related Protein; D010654:Phenylbutyrates; D011719:Pyrazines; D000069286:Bortezomib