Rao Srinivasa R, Edwards Claire M, Edwards James R
Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences University of Oxford Oxford UK.
Nuffield Department of Surgical Sciences University of Oxford Oxford UK.
JBMR Plus. 2020 Mar 23;4(4):e10356. doi: 10.1002/jbm4.10356. eCollection 2020 Apr.
Bone is the most common site for cancer metastasis. Understanding the interactions within the complex, heterogeneous bone-tumor microenvironment is essential for the development of new therapeutics. Various animal models of tumor-induced bone disease are routinely used to provide valuable information on the relationship between cancer cells and the skeleton. However, new model systems exist that offer an alternative approach to the use of animals and might more accurately reveal the cellular interactions occurring within the human bone-tumor niche. This review highlights replacement models that mimic the bone microenvironment and where cancer metastases and tumor growth might be assessed alongside bone turnover. Such culture models include the use of calcified regions of animal tissue and scaffolds made from bone mineral hydroxyapatite, synthetic polymers that can be manipulated during manufacture to create structures resembling trabecular bone surfaces, gel composites that can be modified for stiffness and porosity to resemble conditions in the tumor-bone microenvironment. Possibly the most accurate model system involves the use of fresh human bone samples, which can be cultured ex vivo in the presence of human tumor cells and demonstrate similar cancer cell-bone cell interactions as described in vivo. In addition, the use of mathematical modeling and computational biology approaches provide an alternative to preliminary animal testing. The use of such models offers the capacity to mimic significant elements of the human bone-tumor environment, and complement, refine, or replace the use of preclinical models. © 2020 The Authors. published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
骨是癌症转移最常见的部位。了解复杂、异质性的骨肿瘤微环境中的相互作用对于开发新的治疗方法至关重要。各种肿瘤诱导性骨病的动物模型经常被用于提供关于癌细胞与骨骼之间关系的有价值信息。然而，存在一些新的模型系统，它们提供了一种替代动物使用的方法，并且可能更准确地揭示人类骨肿瘤微环境中发生的细胞相互作用。本综述重点介绍了模拟骨微环境的替代模型，在这些模型中，可以在评估骨转换的同时评估癌症转移和肿瘤生长。此类培养模型包括使用动物组织的钙化区域以及由骨矿物质羟基磷灰石制成的支架、在制造过程中可进行操控以创建类似小梁骨表面结构的合成聚合物、可针对硬度和孔隙率进行改性以模拟肿瘤-骨微环境条件的凝胶复合材料。可能最精确的模型系统涉及使用新鲜的人骨样本，这些样本可以在人肿瘤细胞存在的情况下进行体外培养，并表现出与体内描述的类似的癌细胞-骨细胞相互作用。此外，数学建模和计算生物学方法的使用为初步动物试验提供了一种替代方法。使用此类模型能够模拟人类骨肿瘤环境的重要元素，并补充、完善或替代临床前模型的使用。© 2020作者。由Wiley Periodicals, Inc.代表美国骨与矿物质研究学会出版。
