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Development of a brain metastatic canine prostate cancer cell line

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 microm, respectively. CONCLUSION: The new prostate cancer cell line (Leo) will be a valuable model to investigate the mechanisms of the brain and bone metastases

Keywords : Adrenal Gland Neoplasms,Animals,antagonists & inhibitors,Antineoplastic Agents,Bone Neoplasms,Boronic Acids,Bortezomib,Brain,Brain Neoplasms,Carcinogenicity Tests,Carcinoma,Cell Division,Cell Line,Cell Line,Tumor,Central Nervous System,Dogs,drug effects,epidemiology,Growth,Immunohistochemistry,Incidence,Injections,Subcutaneous,Keratin-18,Keratin-7,Keratin-8,Male,metabolism,methods,Mice,Mice,Nude,Morbidity,mortality,Neoplasm Transplantation,Neoplasms,Connective Tissue,Nervous System,Parathyroid Hormone-Related Protein,pathology,pharmacology,Phenylbutyrates,Prostate,Prostatic Neoplasms,Pyrazines,Radiography,Reverse Transcriptase Polymerase Chain Reaction,secondary,Spinal Cord,Spinal Cord Neoplasms,Subcutaneous Tissue,Transplantation,Heterologous,Universities,, Brain,Metastatic,Canine, back specialist harley street

Date of Publication : 2011 Sep

Authors : Thudi NK;Shu ST;Martin CK;Lanigan LG;Nadella MV;Van BA;Werbeck JL;Simmons JK;Murahari S;Kisseberth WC;Breen M;Williams C;Chen CS;McCauley LK;Keller ET;Rosol TJ;

Organisation : Department of Radiation Oncology, University of Alabama, Birmingham, AL, USA

Journal of Publication : Prostate

Pubmed Link : https://www.ncbi.nlm.nih.gov/pubmed/21321976

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