Epidermal growth factor promotes breast cancer cell chemotaxis in CXCL12 gradients
Epidermal growth factor promotes breast cancer cell chemotaxis in CXCL12 gradients
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DOI：
10.1002/bit.21851
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发表时间：
2008-08-15
影响因子：
3.8
通讯作者：
Jeon, Noo Li
中科院分区：
文献类型：
--
作者：
Mosadegh, Bobak;Saadi, Wajeeh;Jeon, Noo Li
趋化因子受体CXCR4及其配体CXCL12在乳腺癌的侵袭和转移中起重要作用，并诱导多种癌细胞的趋化性。先前对CXCL12诱导趋化性的研究在很大程度上依赖于终点检测（例如，Transwell检测），这些检测对细胞微环境的控制较差。具体而言，这些检测无法剖析自分泌和旁分泌生长因子在趋化因子诱导的癌细胞趋化性中所起的作用。在此，我们使用一种微流控趋化室，它能够直接表征特定外源因素对细胞迁移的影响，而不受自分泌/旁分泌信号的干扰。利用这种方法，我们研究了MDA - MB - 231乳腺癌细胞在明确的CXCL12梯度中的迁移情况。我们发现单独的CXCL12无法刺激这些细胞的趋化性；然而，当CXCL12梯度中补充均匀的表皮生长因子（EGF）刺激或条件培养基时，就会诱导出定向反应。这种对生长因子信号的依赖性表明自分泌和旁分泌因子在决定细胞迁移反应方面的重要性，并且可能在癌症转移中起重要作用。
The chemokine receptor CXCR4 and its ligand CXCL12 play an important role in breast cancer invasion and metastasis, and induce the chemotaxis of various types of cancer cells. Previous studies of CXCL12-induced chemotaxis have, for the most part, relied on endpoint assays (e.g., transwell assays) that provide poor control over the cell microenvironment. Specifically, these assays lacked the ability to dissect the role that autocrine and paracrine growth factors play in chemokine-induced cancer cell chemotaxis. Here, we employ a microfluidic chemotaxis chamber that allows the effects of specific exogenous factors on cell migration to be directly characterized, without the interference of autocrine/paracrine signaling. Using this approach, we investigated the migration of MDA-MB-231 breast cancer cells in well-defined CXCL12 gradients. We found that CXCL12 alone failed to stimulate chemotaxis of these cells; however, when the CXCL12 gradient was supplemented with a uniform stimulus of either EGF or conditioned media, a directional response was induced. This dependence on growth factor signaling points to the importance of autocrine and paracrine factors in determining the migratory response of the cells, and may play an important role in cancer metastasis.