The Prostate · 2011
Development of a brain metastatic canine prostate cancer cell line.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Thudi Nanda K, Shu Sherry T, Martin Chelsea K, Lanigan Lisa G, Nadella Murali V P, Van Bokhoven Adrie, Werbeck Jillian L, Simmons Jessica K, Murahari Sridhar, Kisseberth William C, Breen Matthew, Williams Christina, Chen Ching-Shih, McCauley Laurie K, Keller Evan T, Rosol Thomas J
Аннотация
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.
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.
Предметные рубрики MeSH
Adrenal Gland NeoplasmsAnimalsAntineoplastic AgentsBone NeoplasmsBoronic AcidsBortezomibBrain NeoplasmsCarcinogenicity TestsCarcinomaCell DivisionCell Line, TumorDogsImmunohistochemistryIncidenceInjections, SubcutaneousKeratin-18Keratin-7Keratin-8MaleMiceMice, NudeNeoplasm TransplantationNeoplasms, Connective TissueParathyroid Hormone-Related ProteinPhenylbutyratesProstatic NeoplasmsPyrazinesReverse Transcriptase Polymerase Chain ReactionSpinal Cord NeoplasmsSubcutaneous TissueTransplantation, Heterologous