Implantable pre-metastatic niches for the study of the microenvironmental regulation of disseminated human tumour cells
Implantable pre-metastatic niches for the study of the microenvironmental regulation of disseminated human tumour cells
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DOI：
10.1038/s41551-018-0307-x
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发表时间：
2018-12-01
影响因子：
28.1
通讯作者：
Lee, Jungwoo
中科院分区：
文献类型：
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作者：
Carpenter, Ryan A.;Kwak, Jun-Goo;Lee, Jungwoo
癌症幸存者通常携带播散性肿瘤细胞（DTC）；然而，由于 DTC 休眠，它们不会从治疗中复发。了解局部微环境如何调节 DTC 从静止状态到活跃增殖的转变可能会提出预防或延缓转移形成的新治疗策略。在这里，我们展示了包含人类基质细胞、免疫细胞和癌细胞的可植入生物材料微环境可用于检查肿瘤微环境进化的传播后阶段。植入小鼠皮下后，接种人骨髓基质细胞的多孔水凝胶支架形成血管化生态位，并招募从原位前列腺肿瘤异种移植物中释放的人循环肿瘤细胞。全身注射人外周血单核细胞可减缓早期转移灶的进展。然而，明显转移率没有改变。可植入的转移前生态位为研究 DTC 激活和演变为致死性转移提供了新的机会，并且可以促进有效抗转移疗法的开发。
Survivors of cancer often carry disseminated tumour cells (DTCs); however, they do not relapse from treatment owing to DTC dormancy. Understanding how the local microenvironment regulates the transition of DTCs from a quiescent state to active proliferation could suggest new therapeutic strategies to prevent or delay the formation of metastases. Here, we show that implantable biomaterial microenvironments incorporating human stromal cells, immune cells and cancer cells can be used to examine the post-dissemination phase of tumour microenvironment evolution. After subdermal implantation in mice, porous hydrogel scaffolds seeded with human bone marrow stromal cells form a vascularized niche and recruit human circulating tumour cells released from an orthotopic prostate tumour xenograft. Systemic injection of human peripheral blood mononuclear cells slowed the progression of early metastatic niches. However, the rate of overt metastases did not change. Implantable pre-metastatic niches provide a new opportunity to study DTC activation and evolution to lethal metastasis, and could facilitate the development of effective anti-metastatic therapies.