Development of a brain metastatic canine prostate cancer cell line.

Development of a brain metastatic canine prostate cancer cell line.
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DOI:
10.1002/pros.21341
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发表时间:
2011-09
期刊:
影响因子:
2.8
通讯作者:
Rosol, Thomas J.
Rosol, Thomas J.
中科院分区:
医学3区
文献类型:
--
作者:
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.

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由于转移性疾病,男性前列腺癌具有很高的死亡率和发病率。前列腺癌转移的病理生物学尚不清楚,需要细胞系和动物模型来概括该疾病的复杂性。因此,这项研究的目的是建立和鉴定一种来自患有自发性前列腺癌的狗的新的前列腺癌系。从一只患有自发性前列腺癌的狗身上获得了一种新的细胞系(Leo)。采用免疫组织化学和PCR技术对裸鼠原发性前列腺癌和异种前列腺癌进行了表征。通过生物发光成像、x线摄影和组织病理学观察裸鼠皮下肿瘤的生长和转移情况。体外检测Leo细胞对药物的化学敏感性。Leo细胞表达分泌性上皮细胞角蛋白(CK) 8、18和导管细胞标志物CK7。该细胞系在体外生长(超过75代),在裸鼠皮下具有致瘤性。心内注射后,骨髓细胞转移到脑、脊髓、骨和肾上腺。转移到中枢神经系统的发生率最高(80%),骨(20%)和肾上腺(16%)的发生率较低。体外化学敏感性实验表明,Leo细胞对velcade和HDAC-42抑制剂敏感,IC50浓度分别为1.9 nM和0.95 μM。新的前列腺癌细胞系(Leo)将成为研究脑和骨转移机制的有价值的模型。
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. 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. 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 IC50 concentrations of 1.9 nM and 0.95 μM respectively. The new prostate cancer cell line (Leo) will be a valuable model to investigate the mechanisms of the brain and bone metastases.
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影响因子: 2.4
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