Power Carl A, Pwint Hnin, Chan Jeffrey, Cho Jae, Yu Yan, Walsh William, Russell Pamela J
Oncology Research Centre, Prince of Wales Hospital, Randwick, NSW, Australia.
Prostate. 2009 Nov 1;69(15):1613-23. doi: 10.1002/pros.21010.
Bone metastasis is a frequent and catastrophic consequence of prostate cancer for which only palliative treatment is available. Animal models of bone metastatic prostate cancer are necessary for understanding disease mechanisms but few models exist.
We have used the murine prostate carcinoma cell line RM1 to generate a bone metastatic model of prostate cancer. Repeated intracardiac injection of RM1 cells followed by isolation of cells from bone tumors has yielded a cell line with strong bone-metastatic potential, RM1 bone metastatic (BM).
This cell line metastasizes to multiple bony sites in over 95% of injected C57BL/6 mice and is far less tropic to soft tissues. Bone tumors produced by the RM1(BM) cell line show no preference for particular skeletal sites as most bones are affected. Histology, and micro-computed tomography show that RM1(BM) cells form osteolytic tumors, but with evidence of osteoblastic changes. In vitro the RM1 cells express E-cadherin but not vimentin, do not form colonies in soft agar, are non-invasive but are more motile than the parent cell line.
This model provides a novel means for identifying cellular and molecular mechanisms that contribute to bone metastasis and allow for preclinical testing of therapies to prevent and treat tumor metastasis to bone. Finally as the syngeneic tumor cells are injected into immunocompetent mice, this model will provide a means to study interactions between the immune system, tumors and bone, and therapies that target such interactions.
骨转移是前列腺癌常见且严重的后果，目前仅有姑息治疗手段。骨转移性前列腺癌的动物模型对于理解疾病机制至关重要，但现有的模型很少。
我们使用小鼠前列腺癌细胞系RM1建立了前列腺癌骨转移模型。通过反复心内注射RM1细胞，随后从骨肿瘤中分离细胞，获得了具有强大骨转移潜能的细胞系RM1骨转移（BM）细胞系。
该细胞系在超过95%的注射C57BL/6小鼠中转移至多个骨部位，对软组织的趋向性远低于此。RM1（BM）细胞系产生的骨肿瘤对特定骨骼部位无偏好，大多数骨骼都会受到影响。组织学和微型计算机断层扫描显示，RM1（BM）细胞形成溶骨性肿瘤，但有骨母细胞变化的证据。在体外，RM1细胞表达E-钙黏蛋白但不表达波形蛋白，在软琼脂中不形成集落，无侵袭性，但比亲代细胞系更具运动性。
该模型为识别促成骨转移的细胞和分子机制提供了一种新方法，并允许对预防和治疗肿瘤骨转移的疗法进行临床前测试。最后，由于将同基因肿瘤细胞注射到具有免疫活性的小鼠体内，该模型将提供一种研究免疫系统、肿瘤和骨之间相互作用以及针对此类相互作用的疗法的方法。
