Human 3D vascularized organotypic microfluidic assays to study breast cancer cell extravasation
Human 3D vascularized organotypic microfluidic assays to study breast cancer cell extravasation
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DOI：
10.1073/pnas.1417115112
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发表时间：
2015-01-06
影响因子：
11.1
通讯作者：
Kamm, Roger D.
中科院分区：
文献类型：
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作者：
Jeon, Jessie S.;Bersini, Simone;Kamm, Roger D.
癌症转移的一个关键方面是特定的癌细胞倾向于归巢到次级器官的定义子集。尽管有这些已知的趋势，但对潜在的机制仍然知之甚少。在这里，我们开发了一个微流体3D体外模型，通过与壁细胞同心包裹的微血管网络来分析器官特异性人乳腺癌细胞外渗到骨骼和肌肉模拟微环境中。外渗率和微血管通透性在骨模拟微环境中与未调节或含成肌细胞的基质相比有显著差异。阻断乳腺癌细胞A（3）腺苷受体导致癌细胞向含成纤维细胞基质的外渗率高于未处理细胞，提示腺苷在减少外渗中的作用。这些结果证明了我们的模型作为药物筛选平台和研究癌症生物学中涉及的特定分子途径的有前途的工具的有效性，并具有个性化医疗的潜在应用。
A key aspect of cancer metastases is the tendency for specific cancer cells to home to defined subsets of secondary organs. Despite these known tendencies, the underlying mechanisms remain poorly understood. Here we develop a microfluidic 3D in vitro model to analyze organ-specific human breast cancer cell extravasation into bone- and muscle-mimicking microenvironments through a microvascular network concentrically wrapped with mural cells. Extravasation rates and microvasculature permeabilities were significantly different in the bone- mimicking microenvironment compared with unconditioned or myoblast containing matrices. Blocking breast cancer cell A(3) adenosine receptors resulted in higher extravasation rates of cancer cells into themyoblast-containingmatrices compared with untreated cells, suggesting a role for adenosine in reducing extravasation. These results demonstrate the efficacy of our model as a drug screening platform and a promising tool to investigate specific molecular pathways involved in cancer biology, with potential applications to personalized medicine.