Department of Bioengineering, Stanford University, Stanford, CA, 94305, USA.
Department of Bioengineering, Stanford University, Stanford, CA, 94305, USA.
Biomaterials. 2023 Aug;299:122163. doi: 10.1016/j.biomaterials.2023.122163. Epub 2023 May 18.
Bone is the most common target of metastasis in breast cancer and prostate cancer, leading to significant mortality due to lack of effective treatments. The discovery of novel therapies has been hampered by a lack of physiologically relevant in vitro models that can mimic key clinical features of bone metastases. To fill this critical gap, here we report spatially patterned, tissue engineered 3D models of breast cancer and prostate cancer bone metastasis which mimic bone-specific invasion, cancer aggressiveness, cancer-induced dysregulation of bone remodeling, and in vivo drug response. We demonstrate the potential of integrating such 3D models with single-cell RNA sequencing to identify key signaling drivers of cancer metastasis to bone. Together, these results validate that spatially patterned 3D bone metastasis models mimic key clinical features of bone metastasis and can serve as a novel research tool to elucidate bone metastasis biology and expedite drug discovery.
骨骼是乳腺癌和前列腺癌转移的最常见靶标，由于缺乏有效治疗方法，导致大量患者死亡。新型治疗方法的发现受到缺乏能够模拟骨转移关键临床特征的生理相关体外模型的阻碍。为了填补这一关键空白，我们在这里报告了空间模式化、组织工程化的乳腺癌和前列腺癌骨转移 3D 模型，这些模型模拟了骨特异性浸润、癌症侵袭性、癌症引起的骨重塑失调以及体内药物反应。我们证明了将这种 3D 模型与单细胞 RNA 测序相结合来鉴定癌症转移到骨骼的关键信号驱动因素的潜力。总之，这些结果验证了空间模式化 3D 骨转移模型模拟了骨转移的关键临床特征，并且可以作为一种新的研究工具来阐明骨转移生物学并加速药物发现。
