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

Links

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Publisher Full Text

Authors

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

Institution

Department of Radiation Oncology, University of Alabama, Birmingham, AL, USA.

Source

The Prostate 71:12 2011 Sep pg 1251-63

MeSH

Adrenal Gland Neoplasms
Animals
Antineoplastic Agents
Bone Neoplasms
Boronic Acids
Brain Neoplasms
Carcinogenicity Tests
Carcinoma
Cell Division
Cell Line, Tumor
Dogs
Immunohistochemistry
Incidence
Injections, Subcutaneous
Keratin-18
Keratin-7
Keratin-8
Male
Mice
Mice, Nude
Neoplasm Transplantation
Neoplasms, Connective Tissue
Parathyroid Hormone-Related Protein
Phenylbutyrates
Prostatic Neoplasms
Pyrazines
Reverse Transcriptase Polymerase Chain Reaction
Spinal Cord Neoplasms
Subcutaneous Tissue
Transplantation, Heterologous

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21321976