Implantable pre-metastatic niches for the study of the microenvironmental regulation of disseminated human tumour cells.,Nature Biomedical Engineering

当前位置： X-MOL 学术 › Nat. Biomed. Eng. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Implantable pre-metastatic niches for the study of the microenvironmental regulation of disseminated human tumour cells.
Nature Biomedical Engineering ( IF 26.8 ) Pub Date : 2018-10-22 , DOI: 10.1038/s41551-018-0307-x
Ryan A Carpenter ₁ , Jun-Goo Kwak ₁ , Shelly R Peyton _{1,

2} , Jungwoo Lee _{1,

2}

Affiliation

Cancer survivors often carry disseminated tumour cells (DTCs), yet owing to DTC dormancy they do not relapse from treatment. 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 the evolution of the tumour microenvironment. 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 evolution of the active metastatic niches but did not change the rate of overt metastases, as the ensuing inflammation promoted the formation of DTC colonies. Implantable pre-metastatic niches might enable the study of DTC colonization and proliferation, and facilitate the development of effective anti-metastatic therapies.

中文翻译：

用于研究播散性人类肿瘤细胞的微环境调节的可植入转移前生态位。

癌症幸存者通常携带播散性肿瘤细胞 (DTC)，但由于 DTC 休眠，他们不会因治疗而复发。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减缓了活性转移微环境的进化，但没有改变明显转移的速度，因为随后的炎症促进了 DTC 集落的形成。可植入的转移前生态位可能有助于研究 DTC 定植和增殖，并促进有效抗转移疗法的开发。

更新日期：2019-01-26

点击分享查看原文

点击收藏

公开下载

阅读更多本刊新发论文