Microfabricated mimics of in vivo structural cues for the study of guided tumor cell migration
Microfabricated mimics of in vivo structural cues for the study of guided tumor cell migration
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DOI：
10.1039/c2lc40726d
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发表时间：
2012-01-01
期刊：
影响因子：
6.1
通讯作者：
Hansford, Derek J.
中科院分区：
文献类型：
--
作者：
Gallego-Perez, Daniel;Higuita-Castro, Natalia;Hansford, Derek J.
引导细胞迁移在肿瘤转移中起着至关重要的作用，肿瘤转移被认为是癌症患者死亡的主要原因。这种行为部分地受存在于实质或基质中的微/纳米级地形线索以纤维样和/或导管样结构(例如，白质束、血管/淋巴管、硬膜下和腹膜下间隙)的形式的调节。在本文中，我们使用软光刻微模塑技术开发了一种具有微尺度表面图案的组织培养聚苯乙烯平台，该平台能够诱导引导细胞沿/穿过纤维/导管状结构移动。通过时间推移显微镜在单细胞水平上监测从脑切除的原发肿瘤(胶质瘤)和转移性肿瘤(肺和结肠)的迁移行为。所有肿瘤细胞均呈轴向持续迁移，胶质瘤、肺癌和结肠癌细胞的单向运动细胞百分率分别为84.0±3.5%、58.3±6.8%和69.4±-5.4%。肺肿瘤细胞的迁移速度(41.8+/-4.6µm h(-1))高于胶质瘤(24.0±1.8µm h(-1))和结肠癌(26.7+/-2.8µm h(-1))。该平台有可能与其他生物检测方法联合使用，以探索引导细胞迁移条件下转移表型的潜在机制，并可能单独作为针对特定肿瘤细胞运动行为的治疗有效性的指标。
Guided cell migration plays a crucial role in tumor metastasis, which is considered to be the major cause of death in cancer patients. Such behavior is regulated in part by micro/nanoscale topographical cues present in the parenchyma or stroma in the form of fiber-like and/or conduit-like structures (e. g., white matter tracts, blood/lymphatic vessels, subpial and subperitoneal spaces). In this paper we used soft lithography micromolding to develop a tissue culture polystyrene platform with a microscale surface pattern that was able to induce guided cell motility along/through fiber-/conduit-like structures. The migratory behaviors of primary (glioma) and metastatic (lung and colon) tumors excised from the brain were monitored via time-lapse microscopy at the single cell level. All the tumor cells exhibited axially persistent cell migration, with percentages of unidirectionally motile cells of 84.0 +/- 3.5%, 58.3 +/- 6.8% and 69.4 +/- 5.4% for the glioma, lung, and colon tumor cells, respectively. Lung tumor cells showed the highest migratory velocities (41.8 +/- 4.6 mu m h(-1)) compared to glioma (24.0 +/- 1.8 mu m h(-1)) and colon (26.7 +/- 2.8 mu m h(-1)) tumor cells. This platform could potentially be used in conjunction with other biological assays to probe the mechanisms underlying the metastatic phenotype under guided cell migration conditions, and possibly by itself as an indicator of the effectiveness of treatments that target specific tumor cell motility behaviors.