Epithelial cell guidance by self-generated EGF gradients.
Epithelial cell guidance by self-generated EGF gradients.
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DOI：
10.1039/c2ib00106c
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发表时间：
2012-03
期刊：
影响因子：
--
通讯作者：
Irimia D
中科院分区：
文献类型：
--
作者：
Scherber C;Aranyosi AJ;Kulemann B;Thayer SP;Toner M;Iliopoulos O;Irimia D
癌上皮细胞通常从原发肿瘤迁移到周围组织中。它们的迁移通常被认为是由靶组织中预先存在的趋化因子和生长因子的空间梯度引导的。然而，出乎意料的是，我们发现，上皮细胞的引导迁移是可能的，在体外的预先存在的化学梯度的情况下。我们观察到正常和癌上皮细胞都可以持续迁移，并从充满均匀浓度培养基的显微迷宫中沿着沿着到达出口。使用微尺度工程技术和生物物理模型，我们发现了一种自我指导策略，在此期间，上皮细胞在生化限制的条件下产生自己的指导线索。自我引导策略取决于三个相互依赖的过程之间的平衡：细胞对表皮生长因子（EGF）的摄取（U），EGF通过结构化微环境的限制性运输（T），以及细胞对所得EGF梯度的趋化性（C）。UTC自我指导策略可以通过抑制EGF受体的信号传导而受到干扰，并且似乎独立于趋化因子信号传导。更好地理解UTC自我指导策略最终可以帮助设计调节上皮细胞迁移和延迟癌细胞侵袭或加速伤口愈合的新方法。
Cancer epithelial cells often migrate away from the primary tumor to invade into the surrounding tissues. Their migration is commonly assumed to be directed by pre-existent spatial gradients of chemokines and growth factors in the target tissues. Unexpectedly however, we found that the guided migration of epithelial cells is possible in vitro in the absence of pre-existent chemical gradients. We observed that both normal and cancer epithelial cells can migrate persistently and reach the exit along the shortest path from microscopic mazes filled with uniform concentrations of media. Using microscale engineering techniques and biophysical models, we uncovered a self-guidance strategy during which epithelial cells generate their own guiding cues under conditions of biochemical confinement. The self-guidance strategy depends on the balance between three interdependent processes: epidermal growth factor (EGF) uptake by the cells (U), the restricted transport of EGF through the structured microenvironment (T), and cell chemotaxis toward the resultant EGF gradients (C). The UTC self-guidance strategy can be perturbed by inhibition of signalling through EGF-receptors and appears to be independent from chemokine signalling. Better understanding of the UTC self-guidance strategy could eventually help devise new ways for modulating epithelial cell migration and delaying cancer cell invasion or accelerating wound healing.
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影响因子：
8.8
作者：
Okubo, S;Kurebayashi, J;Otsuki, T;Yamamoto, Y;Tanaka, K;Sonoo, H
通讯作者：
Sonoo, H
影响因子：
2.5
作者：
Ambravaneswaran, Vijayakrishnan;Wong, Ian Y.;Irimia, Daniel
通讯作者：
Irimia, Daniel
影响因子：
--
作者：
Shibata, T;Kawano, T;Hosokawa, M
通讯作者：
Hosokawa, M
影响因子：
3.4
作者：
Haugh, JM
通讯作者：
Haugh, JM
影响因子：
64.8
作者：
Karnoub, Antoine E.;Dash, Ajeeta B.;Weinberg, Robert A.
通讯作者：
Weinberg, Robert A.