癌症细胞“跑”之前要学“走”

　　生物通报道：来自萨克生物研究学院（the Salk Institute for Biological Studies）分子与细胞生物学实验室的研究人员发现早期阶段，未侵入周遍组织的乳腺癌细胞也许已经包含有了高运动性的细胞，为肿瘤进行转移扩散做好准备。这说明这些细胞虽然没有侵入，但是已经在乳管（milk ducts，生物通注）中“徘徊”，在这些乳腺中埋下新肿瘤的的“导火线”。这一研究成果公布在12月30日的《Journal of Cell Biolo》杂志上。

文章的通讯作者是萨克研究院的分子与细胞生物学教授，第一作者是Gray W. Pearson，他解释道，“没有侵入也意味着没有运动性，但是在这里并不是这样。”

Tony Hunter表示，“这是一项令人激动的发现，因为这说明细胞也许比我们之前想象的要早一些就具有了迁移的特性。”

由于增加了筛选的程序，大部分的乳腺癌肿瘤在其还尚小和未扩散之前就已经被检测了出来，在这些病例中，癌症细胞还并未向周遍组织扩散，限制在duct中——duct是最常见的乳腺癌侵入开始的位置，这些肿瘤就是我们已知的导管原位癌（ductal carcinoma in si-tu，DCIS，生物通注）。

导管原位癌的标准治疗是切除（lumpectomy，生物通注），即利用外科手段将肿瘤和周遍组织切除。但是通过切除进行治疗的DCIS患者大约15%在5年之后都会复发，这其中的一个问题就是这些病患是否需要在手术后增加放疗的治疗，目前这一判断的标准主要是依靠肿瘤的大小尺寸。

Pearson认为，“我们的发现说明，如果DCIS具有这些高运动性细胞，那么病患也许就增加了复发的危险性”，“因此也许无论肿瘤的大小，都需要增加放疗。”

虽然这些高运动性细胞也许在未来能指导治疗决定，但是Pearson也警告道，研究人员目前还不肯定这些游移的细胞确实会影响一个病患的治疗效果。

在这项研究中，研究人员利用一种能恢复乳腺管的组织培养模型进行研究，他们将从乳腺组织中分离得到的人类细胞导入道一种三维基质中，模拟其天然的生长环境，这些细胞能自然发育成所谓的腺胞（acinus，生物通注）——与小乳管相似的中空结构。

之后研究人员开启了ERK1/2 MAP kinase途径（一种在肿瘤发育过程中时常呈现出活跃状态的级联放大信号系统，生物通注），并且实时进行跟踪，观测乳腺癌细胞如何学会“走”，“我们很快意识到这其中以后一个重要的细胞运动过程，这让我们十分惊讶”，Pearson说，“在24小时中，许多这些球状泡会失去其原有的组织体，细胞开始舞蹈”，“在侵入之前获得运动性建娣了未来侵入生长的障碍”。

Hunter表示，“利用活细胞成像能帮助我们观测到组织中经标记的细胞，了解它们的行为特征，这在培养细胞中是不能得知的”。下一步，研究人员希望能分辩出乳腺癌细胞运动的分子标记，从而帮助肿瘤学家治疗具有高度扩散危险性的病患。
（生物通：张迪）

原文摘要：
Published online 31 December 2007
doi:10.1083/jcb.200706099
The Journal of Cell Biology, Vol. 179, No. 7, 1555-1567
Real-time imaging reveals that noninvasive mammary epithelial acini can contain motile cells
『Abstract』

附：
美国加州：萨克生物研究学院 (Salk Institute for Biological Studies)

【简介】
Jonas Salk, the developer of the polio vaccine, established the Salk Institute for Biological Studies more than 40 years ago. His goal was to create an institute that would serve as a "crucible for creativity" to pursue questions about the basic principles of life. He wanted biologists and others to work together to explore the wider implications of their discoveries for the future of humanity.

In 1959, Salk and architect Louis Kahn began a unique partnership to design a truly distinguished research facility. Seed money was provided by the March of Dimes, which has continuously and generously supported the Salk Institute over its history. The San Diego City Council gifted the Institute with the land on which to build the facility, and this decision was approved and affirmed overwhelmingly by the people of San Diego in a special referendum.

Today, the Salk Institute conducts its biological research under the guidance of 56 faculty investigators, employing a scientific staff of more than 850, including visiting scientists, postdoctoral fellows, and graduate students. This group, recruited throughout the world, receives advice from nine distinguished nonresident fellows—influential scientists at similar institutions throughout the world.

Major areas of study focus within three areas: Molecular Biology and Genetics; Neurosciences; and Plant Biology. Knowledge acquired in Salk laboratories provides new understanding and potential new therapies and treatments for a range of diseases—from cancer to AIDS, from Alzheimer’s disease to cardiovascular disorders, from anomalies of the brain to birth defects. Studies in plant biology at the Salk may one day help improve the quality and quantity of the world’s food supply.

With the completion of the Human Genome Project, the Salk Institute is strengthening its existing programs while also moving in exciting new directions. Six key areas represent strategic research priorities: Chemistry and Proteomics; Stem Cell Biology; Cell Biology; Regulatory Biology; Metabolic Research; and Computational and Theoretical Biology.

The Salk Institute consistently ranks among the leading research institutions in the world in objective measures of the contributions of faculty and the impact of their findings. The Institute has trained more than 2,000 scientists, many of whom have gone on to positions of leadership in other prominent research centers worldwide. Five scientists trained at the Institute have won Nobel prizes, and four current resident faculty members are Nobel Laureates.

Jonas Salk's vision, coupled with the hard work and dedication of former and present Salk investigators has resulted in a unique environment where scientific discoveries have an important impact on our understanding of human health.

Basic research is truly "where cures begin ." Discoveries of the principles governing cellular activity have frequently illuminated the path toward therapies and cures. In this, Jonas Salk’s noble vision impels us still.