Spatially patterned 3D model mimics key features of cancer metastasis to bone.
Spatially patterned 3D model mimics key features of cancer metastasis to bone.
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DOI：
10.1016/j.biomaterials.2023.122163
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发表时间：
2023-05
期刊：
影响因子：
14
通讯作者：
Eva C. González Díaz;Michelle Tai;Callan E Monette;Joy Wu;Fan Yang
中科院分区：
文献类型：
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作者：
Eva C. González Díaz;Michelle Tai;Callan E Monette;Joy Wu;Fan Yang
在乳腺癌和前列腺癌中，骨是最常见的转移靶点，由于缺乏有效的治疗方法，导致大量死亡。由于缺乏能够模拟骨转移关键临床特征的生理学相关体外模型，新疗法的发现一直受到阻碍。为了填补这一关键空白，我们在这里报告了乳腺癌和前列腺癌骨转移的空间图案化、组织工程化3D模型，该模型模拟了骨特定的侵袭、癌症侵袭性、癌症诱导的骨重建失调以及体内药物反应。我们展示了将这种3D模型与单细胞RNA测序相结合的潜力，以确定癌症转移到骨的关键信号驱动因素。综上所述，这些结果验证了空间模式的3D骨转移模型模拟了骨转移的关键临床特征，并可以作为一种新的研究工具来阐明骨转移生物学和加快药物开发。
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.