Tsingotjidou Anastasia S, Ahluwalia Raj, Zhang Xuguang, Conrad Heather, Emmanouilides Christos
Division of Diagnostic and Surgical Sciences, UCLA School of Dentistry, CA 90095, USA.
Int J Oncol. 2003 Dec;23(6):1569-74.
The purpose of this study was to develop a model that investigates the biology of prostate cancer (PCA) that is metastatic to the bone, while closely approximates the clinical presentation of this disease. Human prostate cancer PC-3 cells were transfected with the neolacZ retrovirus. Then, eight-week-old SCID mice were injected subcutaneously with a single dose of PC-3 neolacZ cells. When the mice developed tumors at the injection site, they were sacrificed to harvest tumor fragments. One tumor fragment from a single PC-3 neolacZ injected animal was implanted into the prostates of five SCID mice. The SCID mice had all been previously grafted with adult human bone. Mice were sacrificed and tumor growth and metastasis to murine tissues as well as to the human bone graft were sought. The histologic samples were stained with X-Gal. In three mice tumors metastasized to the skeletal system. One animal showed limited X-Gal staining of the cells surrounding the human bone implant. In two mice tumors metastasized to liver and kidney and one metastasized to the lung. In this study we established a spontaneous bone metastasis model of human PCA cells with the combination of lacZ expression and orthotopic implantation of the PC-3 implanted tumor fragments. This model offers potential advantages in monitoring the metastatic pattern and behavior of prostate cancer and may be used to selectively study its interaction with human bone.
本研究的目的是建立一个模型，用于研究已发生骨转移的前列腺癌（PCA）的生物学特性，同时紧密模拟该疾病的临床表现。将新霉素乳糖操纵子基因（neolacZ）逆转录病毒转染人前列腺癌PC-3细胞。然后，给8周龄的重症联合免疫缺陷（SCID）小鼠皮下注射单剂量的PC-3-neolacZ细胞。当小鼠在注射部位出现肿瘤时，将其处死以获取肿瘤组织块。从一只注射了PC-3-neolacZ细胞的动物身上获取的一个肿瘤组织块，植入五只SCID小鼠的前列腺中。这些SCID小鼠先前均已移植了成人的骨骼。处死小鼠后，观察肿瘤在小鼠组织以及人骨移植物中的生长和转移情况。组织学样本用X-Gal染色。在三只小鼠中，肿瘤转移至骨骼系统。一只动物的人骨植入物周围细胞显示出有限的X-Gal染色。在两只小鼠中，肿瘤转移至肝脏和肾脏，一只转移至肺。在本研究中，我们通过结合lacZ表达和PC-3植入肿瘤组织块的原位植入，建立了人PCA细胞的自发性骨转移模型。该模型在监测前列腺癌的转移模式和行为方面具有潜在优势，可用于选择性地研究其与人类骨骼的相互作用。
