Rapid chemokinetic movement and the invasive potential of lung cancer cells; a functional molecular study.
Rapid chemokinetic movement and the invasive potential of lung cancer cells; a functional molecular study.
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DOI：
10.1186/1471-2407-6-151
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发表时间：
2006-06-07
期刊：
影响因子：
3.8
通讯作者：
Soon LL
中科院分区：
文献类型：
--
作者：
Tchou-Wong KM;Fok SY;Rubin JS;Pixley F;Condeelis J;Braet F;Rom W;Soon LL
非小细胞肺癌是西方国家恶性疾病早期死亡的最常见原因。这些细胞的异质性已通过组织化学和微阵列生物标志物分析进行了鉴定。不幸的是，用作侵袭和转移模型的细胞系内的形态、分子和生物学变异尚不清楚。在这项研究中，我们测试了这样的假设：异质癌细胞表现出可变的运动反应，例如可以进行分子表征的趋化作用和趋化性。从博伊登室收获并培养在趋化动力学（无梯度）条件下迁移的称为 KINE 的 H460 肺癌细胞亚群。然后进行延时显微镜检查、免疫荧光显微镜检查和微阵列分析，将趋化动力学 KINE 细胞与未选择的 CON 细胞群进行比较。延时显微镜和分析表明，KINE 细胞比未选择的对照群体 (CON) 移动更快，但方向性较差，证实了它们的趋化动力学特征。值得注意的是，趋化 KINE 细胞也能有效趋化。 KINE 细胞与 CON 细胞相比，对基质的粘附性较差，并且表现出前缘成熟粘着斑的丧失以及非聚焦皮质肌动蛋白的存在。这些特征在高运动性变形虫细胞中很常见，可能有利于更快的运动速度。与 CON 相比，KINE 细胞的侵袭性也明显更强。基因阵列研究和实时 PCR 显示，与主要趋化性 CON 细胞相比，高度趋化性 KINE 中一种名为 ROM 的基因下调。与正常肺细胞相比，ROM 在一组肺癌细胞系中的表达也有所减少。这项研究表明，在趋化作用和趋化作用方面均有效的癌细胞表现出高侵袭水平。这些细胞具有与其他细胞群不同的形态、细胞骨架和粘附特性，这些细胞仅在趋化性方面有效，表明极性丧失。了解细胞运动背景下极性的调节对于改善侵袭和转移的控制和抑制非常重要。
Non-small cell lung cancer is the most common cause of early casualty from malignant disease in western countries. The heterogeneous nature of these cells has been identified by histochemical and microarray biomarker analyses. Unfortunately, the morphological, molecular and biological variation within cell lines used as models for invasion and metastasis are not well understood. In this study, we test the hypothesis that heterogeneous cancer cells exhibit variable motility responses such as chemokinesis and chemotaxis that can be characterized molecularly. A subpopulation of H460 lung cancer cells called KINE that migrated under chemokinetic (no gradient) conditions was harvested from Boyden chambers and cultured. Time-lapsed microscopy, immunofluorescence microscopy and microarray analyses were then carried out comparing chemokinetic KINE cells with the unselected CON cell population. Time-lapsed microscopy and analysis showed that KINE cells moved faster but less directionally than the unselected control population (CON), confirming their chemokinetic character. Of note was that chemokinetic KINE cells also chemotaxed efficiently. KINE cells were less adhesive to substrate than CON cells and demonstrated loss of mature focal adhesions at the leading edge and the presence of non-focalized cortical actin. These characteristics are common in highly motile amoeboid cells that may favour faster motility speeds. KINE cells were also significantly more invasive compared to CON. Gene array studies and real-time PCR showed the downregulation of a gene called, ROM, in highly chemokinetic KINE compared to mainly chemotactic CON cells. ROM was also reduced in expression in a panel of lung cancer cell lines compared to normal lung cells. This study shows that cancer cells that are efficient in both chemokinesis and chemotaxis demonstrate high invasion levels. These cells possess different morphological, cytoskeletal and adhesive properties from another population that are only efficient at chemotaxis, indicating a loss in polarity. Understanding the regulation of polarity in the context of cell motility is important in order to improve control and inhibition of invasion and metastasis.
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影响因子：
7.8
作者：
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影响因子：
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影响因子：
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