McCabe N Patrick, Madajka Maria, Vasanji Amit, Byzova Tatiana V
Department of Molecular Cardiology, NB50, The Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USA.
Clin Exp Metastasis. 2008;25(5):581-90. doi: 10.1007/s10585-008-9175-1. Epub 2008 May 28.
The molecular mechanisms associated with prostate cancer (PCa) progression within bone remain a topic of intense investigation. With the availability of transgenic mouse strains, a model of PCa for use in immune competent/transgenic mice would be highly beneficial. This study was designed to explore the utility of RM1 mouse PCa cells in investigations of tumor:bone interactions. The efficacies of several implantation techniques were examined for reliably producing intra-bone RM1 tumor growth and bone lesion formation in immune competent mice. Longitudinal monitoring of bone remodeling and lesion phenotypes was conducted by microcomputed tomography (muCT) and histological analyses. Our results indicate that direct intrabone injections of RM1 cells are necessary for tumor growth within bone and direct implantation promotes the rapid development of osteolytic bone lesions with periosteal bone deposition post-cortical breach. In vitro, RM1 cells promote the proliferation of osteoblast (MC3T3-E1) and osteoclast (Raw264.7) progenitors in a dose dependent manner. Conditioned culture media from RM1 cells appears to promote earlier expression of genes/proteins associated with osteoblastic differentiation. While clearly stimulating osteoclast function in vivo, RM1 cells had little effect on differentiation and tartate resistant acid phosphatase (TRAP) expression by Raw264.7 cells. These data, coupled with in vivo muCT images, indicate the ability of RM1 cells to induce mixed, yet predominentally osteolytic, responses in bone and illustrate the potential of RM1 cells as a model of investigating prostate tumor:stroma interactions in immune competent/transgenic mice on a C57BL/6 background.
与前列腺癌（PCa）在骨内进展相关的分子机制仍是一个深入研究的课题。随着转基因小鼠品系的可得性，一种用于免疫健全/转基因小鼠的PCa模型将非常有益。本研究旨在探索RM1小鼠PCa细胞在肿瘤与骨相互作用研究中的效用。研究了几种植入技术在免疫健全小鼠中可靠产生骨内RM1肿瘤生长和骨病变形成的效果。通过微型计算机断层扫描（μCT）和组织学分析对骨重塑和病变表型进行纵向监测。我们的结果表明，直接骨内注射RM1细胞是骨内肿瘤生长所必需的，直接植入促进溶骨性骨病变的快速发展，并在皮质突破后伴有骨膜骨沉积。在体外，RM1细胞以剂量依赖的方式促进成骨细胞（MC3T3-E1）和破骨细胞（Raw264.7）祖细胞的增殖。来自RM1细胞的条件培养基似乎促进与成骨细胞分化相关的基因/蛋白质的早期表达。虽然RM1细胞在体内明显刺激破骨细胞功能，但对Raw264.7细胞的分化和抗酒石酸酸性磷酸酶（TRAP）表达影响很小。这些数据，再加上体内μCT图像，表明RM1细胞能够在骨中诱导混合但主要为溶骨性的反应，并说明了RM1细胞作为在C57BL/6背景的免疫健全/转基因小鼠中研究前列腺肿瘤与基质相互作用模型的潜力。
