The effects of monocytes on tumor cell extravasation in a 3D vascularized microfluidic model.
The effects of monocytes on tumor cell extravasation in a 3D vascularized microfluidic model.
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DOI：
10.1016/j.biomaterials.2018.03.005
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发表时间：
2019-04
期刊：
影响因子：
14
通讯作者：
Kamm RD
中科院分区：
文献类型：
--
作者：
Boussommier-Calleja A;Atiyas Y;Haase K;Headley M;Lewis C;Kamm RD
转移是癌症相关死亡的主要原因。癌症免疫疗法的最新进展显示出对转移性患者令人兴奋的治疗前景。虽然大多数疗法针对的是T细胞，但其他免疫细胞，如单核细胞，对治疗干预有很大的希望。在我们的研究中，我们在一个三维血管化的微流体模型中提供了人类单核细胞和肿瘤细胞直接接触的主要证据。我们首先描述了我们的模型的新应用，以高分辨率调查和可视化单核细胞从血管内迁移到血管外微环境的演变。我们还在我们的人类模型中证明了它们向巨噬细胞的分化。我们的模型复制了不同单核细胞亚群之间的生理差异。特别是，我们报告炎症，而不是巡逻，单核细胞依赖于基于肌动球蛋白的运动。最后，我们利用这个平台来研究单核细胞在其生命周期的不同阶段对癌细胞外渗的影响。我们的数据表明，单核细胞可以以非接触依赖的方式直接减少癌细胞外渗。相比之下，我们发现单核细胞在通过脉管系统迁移时对癌细胞外渗的影响很小，并且单核细胞呈巨噬细胞样。综上所述，我们的研究为单核细胞在癌细胞外渗中的作用带来了新的见解，这是转移级联的重要步骤。这些发现使我们的微流控平台成为研究单核细胞和单核细胞源性巨噬细胞在正常和病变状态下的特征和功能的有力工具。我们提出，单核细胞与癌细胞的相互作用可以靶向增强我们在体外观察到的抗转移效应，可能扩大可用于抑制转移的免疫疗法的环境。
Metastasis is the leading cause of cancer-related deaths. Recent developments in cancer immunotherapy have shown exciting therapeutic promise for metastatic patients. While most therapies target T cells, other immune cells, such as monocytes, hold great promise for therapeutic intervention. In our study, we provide primary evidence of direct engagement between human monocytes and tumor cells in a 3D vascularized microfluidic model. We first characterize the novel application of our model to investigate and visualize at high resolution the evolution of monocytes as they migrate from the intravascular to the extravascular micro-environment. We also demonstrate their differentiation into macrophages in our all-human model. Our model replicates physiological differences between different monocyte subsets. In particular, we report that inflammatory, but not patrolling, monocytes rely on actomyosin based motility. Finally, we exploit this platform to study the effect of monocytes, at different stages of their life cycle, on cancer cell extravasation. Our data demonstrates that monocytes can directly reduce cancer cell extravasation in a non-contact dependent manner. In contrast, we see little effect of monocytes on cancer cell extravasation once monocytes transmigrate through the vasculature and are macrophage-like. Taken together, our study brings novel insight into the role of monocytes in cancer cell extravasation, which is an important step in the metastatic cascade. These findings establish our microfluidic platform as a powerful tool to investigate the characteristics and function of monocytes and monocyte-derived macrophages in normal and diseased states. We propose that monocyte-cancer cell interactions could be targeted to potentiate the anti-metastatic effect we observe in vitro, possibly expanding the milieu of immunotherapies available to tame metastasis.
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影响因子：
11.2
作者：
Charafe-Jauffret E;Ginestier C;Iovino F;Wicinski J;Cervera N;Finetti P;Hur MH;Diebel ME;Monville F;Dutcher J;Brown M;Viens P;Xerri L;Bertucci F;Stassi G;Dontu G;Birnbaum D;Wicha MS
通讯作者：
Wicha MS
DOI：
10.1038/nrc.2016.97
发表时间：
2016-08-23
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Fesnak AD;June CH;Levine BL
通讯作者：
Levine BL
影响因子：
3
作者：
Carrion, Bita;Janson, Isaac A.;Putnam, Andrew J.
通讯作者：
Putnam, Andrew J.
DOI：
10.1039/c3ib40149a
发表时间：
2013-10
期刊：
Integrative biology : quantitative biosciences from nano to macro
影响因子：
--
作者：
Chen MB;Whisler JA;Jeon JS;Kamm RD
通讯作者：
Kamm RD
影响因子：
4.4
作者：
Collison, Joanna L.;Carlin, Leo M.;Peakman, Mark
通讯作者：
Peakman, Mark