细胞迁移/侵袭试验及其在抗癌药物发现中的应用。

Suzanne A Eccles, Carol Box, William Court
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引用次数: 115

摘要

侵袭能力是区分良性和恶性病变的最重要的特征。肿瘤细胞在血液和淋巴通道的内渗和外渗过程中,以及在继发部位建立集落时,必须穿过正常成年细胞(例如活化的白细胞除外)无法穿过的组织边界。在新血管生成过程中,激活的内皮细胞也利用了类似的机制,使肿瘤能够持续生长和扩散。现在越来越多的人认识到,这些过程——细胞运动和侵袭——可能为癌症治疗提供丰富的新靶点来源,适当的抑制剂可能抑制转移和新血管生成。这种新模式要求筛选分析能够快速定量地测量细胞运动和穿越生理障碍的能力。我们还需要考虑简单的体外还原方法是否可以可靠地模拟体内肿瘤侵袭/新血管生成的复杂性。在发展一种平衡的检测组合,能够准确评估并最终提供具有临床治疗潜力的新型抗侵入药物方面,机遇和挑战并存。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Cell migration/invasion assays and their application in cancer drug discovery.

Invasive capacity is the single most important trait that distinguishes benign from malignant lesions. Tumour cells, during intravasation and extravasation of blood and lymphatic channels and when establishing colonies at secondary sites, must move through tissue boundaries that normal adult cells (other than, for example activated leukocytes) do not cross. Similar mechanisms are also utilised by activated endothelial cells during the generation of new blood vessels that enable the sustained growth and dissemination of tumours. It is now increasingly recognised that these processes--cell motility and invasion--might provide a rich source of novel targets for cancer therapy and that appropriate inhibitors may restrain both metastasis and neoangiogenesis. This new paradigm demands screening assays that can rapidly and quantitatively measure cell movement and the ability to traverse physiological barriers. We also need to consider whether simple reductionist in vitro approaches can reliably model the complexity of in vivo tumour invasion/neoangiogenesis. There are both opportunities and challenges ahead in developing a balanced portfolio of assays that will be able to evaluate accurately and finally deliver novel anti-invasive agents with therapeutic potential for clinical use.

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