Saadi Wajeeh, Wang Shur-Jen, Lin Francis, Jeon Noo Li
Department of Biomedical Engineering, University of California, Irvine, 3120 Natural Sciences II, 92697, USA.
Biomed Microdevices. 2006 Jun;8(2):109-18. doi: 10.1007/s10544-006-7706-6.
Growth factor-induced chemotaxis of cancer cells is believed to play a critical role in metastasis, directing the spread of cancer from the primary tumor to secondary sites in the body. Understanding the mechanistic and quantitative behavior of cancer cell migration in growth factor gradients would greatly help in future treatment of metastatic cancers. Using a novel microfluidic chemotaxis chamber capable of simultaneously generating multiple growth factor gradients, we examined the migration of the human metastatic breast cancer cell line MDA-MB-231 in various conditions. First, we quantified and compared the migration in two gradients of epidermal growth factor (EGF) spanning different concentrations: 0-50 ng/ml and 0.1-6 ng/ml. Cells showed a stronger response in the 0-50 ng/ml gradient. However, the fact that even a shallow gradient of EGF can induce chemotaxis, and that EGF can direct migration over a large dynamic range of gradients, confirms the potency of EGF as a chemoattractant. Second, we investigated the effect of antibody against the EGF receptor (EGFR) on MDA-MB-231 chemotaxis. Quantitative analysis indicated that anti-EGFR antibody impaired both motility and directional orientation (CI = 0.03, speed = 0.71 microm/min), indicating that cell motility was induced by the activation of EGFR. The ability to compare, in terms of quantitative parameters, the effects of different pharmaceutical inhibitors, as well as subtle differences in experimental conditions, will aid in our understanding of mechanisms that drive metastasis. The microfluidic chamber described in this work will provide a platform for cell-based assays that can be used to compare the effectiveness of different pharmaceutical compounds targeting cell migration and metastasis.
生长因子诱导的癌细胞趋化作用被认为在转移过程中起着关键作用，它引导癌症从原发性肿瘤扩散到身体的继发性部位。了解癌细胞在生长因子梯度中的迁移机制和定量行为将极大地有助于未来转移性癌症的治疗。我们使用一种能够同时产生多个生长因子梯度的新型微流控趋化室，在各种条件下检测了人转移性乳腺癌细胞系MDA-MB-231的迁移。首先，我们对表皮生长因子（EGF）的两个不同浓度梯度（0-50 ng/ml和0.1-6 ng/ml）中的迁移进行了定量和比较。细胞在0-50 ng/ml梯度中表现出更强的反应。然而，即使是浅梯度的EGF也能诱导趋化作用，并且EGF能在很大的梯度动态范围内引导迁移，这一事实证实了EGF作为趋化因子的效力。其次，我们研究了抗表皮生长因子受体（EGFR）抗体对MDA-MB-231趋化作用的影响。定量分析表明，抗EGFR抗体损害了细胞的运动性和定向性（趋化指数CI = 0.03，速度 = 0.71微米/分钟），这表明细胞运动性是由EGFR的激活所诱导的。能够根据定量参数比较不同药物抑制剂的效果以及实验条件的细微差异，将有助于我们理解驱动转移的机制。本文所述的微流控室将为基于细胞的检测提供一个平台，可用于比较针对细胞迁移和转移的不同药物化合物的有效性。
