生物谷报道：法国居里研究所、以色列Weizmann科学研究所和德国Technischen大学的研究人员，合力研究一种名为fascin的蛋白在肠癌扩散中所扮演的角色。
居里研究所Danijela Vignjevic说：“癌细胞获得运动和入侵其它组织的能力后开始转移。与所有能运动的细胞一样，这种新行为依赖于感官细胞器丝状伪足（filopodia）感觉环境，帮助细胞决定运动方向。”研究结果刊登于《Cell Migration》。
“Fascin是丝状伪足的关键成分，在肠癌细胞内部，是导致许多基因活化某回路的靶标。”研究人员发现，在肿瘤发展的过程中，fascin的水平也在上升。体外检测显示fascin促进细胞迁移和入侵，体内实验证实fascin与转移有关。Fascin在细胞支架的形成过程中发挥关键作用，因此影响细胞的运动方式。研究人员还发现肿瘤扩散到次级位点后，fascin不再有活性。
Vignjevic与其同事打算制作一个肠癌转移的转基因小鼠模型，以获得更多信息。一位研究人员强调卵巢癌只有在特定信号刺激下才开始迁移。约翰霍普金斯大学Denise Montell教授解释说表皮卵巢癌出现在卵巢特别是覆盖卵巢外表面的细胞，控制这些细胞的机制与控制肿瘤细胞的机制类似。表皮细胞的迁移方式与癌细胞的迁移方式类似，并且这种运动与细胞对周围环境的信号的反应高度协调一致。利用小鼠模型，研究人员鉴别出三种信号。甾类激素决定细胞开始迁移的时间，生长因子决定细胞迁移的方向，细胞运动的能力离不开细胞因子的运动。Montell教授说：“每种信号都要相互协作，才能使细胞朝正确方向移动。但它们并不是唯一的。我们发现Par-1基因调节细胞与表皮的分离，以及原始组织释放细胞的一个关键步骤。”这项发现为药物制造商设计治疗卵巢癌的新药提供了参考。
英文原文：
New insights in cancer cell migration
By Mike Nagle
14/05/2007 - A workshop being held this week in Italy has shed new light on how cancer cells spread around the body, highlighting new strategies for potentially combating the disease.
Researchers from the Institut Curie in France, the Weizmann Institute of Science in Israel and the Technischen Universitat in Germany teamed up to investigate the role of a certain protein called fascin in the spread of colorectal cancer.
"Cancer cells become metastatic because they acquire the ability to move and to invade other tissues. Like all the cells that able to move, this new behaviour relies on sensory organelles called filopodia that sense the environment and help the cells to decide where to go," explained Danijela Vignjevic from the Institute Curie, who presented the research at the Workshop on Cell Migration: from molecules to organisms and diseases, held in Milan.
"Fascin is a key component of filopodia, and, inside the colorectal cancer cells, it represents the target of a circuitry that leads to the activation of several genes."
The team discovered that as the tumour progresses, levels of fascin also increase. In vitro tests showed that it promotes cell migration and invasion, and in vivo experiments confirmed a link between the protein and metastasis.
Fascin plays a key role in the formation of a cell's scaffolding, which in turn affects how mobile it is. The scientists also noticed that once the tumour has spread to a secondary site, fascin is no longer active - once its job is done, its gene is turned off until it is needed again.
Vignjevic and colleagues now hope to generate a transgenic mouse model for colorectal cancer metastasis, which could provide further information into the mechanism of the disease.
However, one of the workshop organisers warned that, although it is tempting to speculate about future therapies, more investigation will be needed "before we can think of moving from bench to bedside".
A second presentation at the workshop highlighted how ovarian cancer cells respond to specific signals to begin migrating. Professor Denise Montell, at the Johns Hopkins University School of Medicine in Baltimore, US, explained that epithelial ovarian cancer develops in the ovary, especially in the cells that cover the outer surface of this organ and these cells are regulated by similar signals to tumour cells.
"Epithelial cells migrate in a way that is reminiscent of the migratory behaviour of cancer cells and this moving is highly coordinated as it responds to extracellular signals present in the surrounding microenvironment. Using our experimental model we were able to identify three kinds of signals," she said.
The team found that steroid hormones dictate the time when cells must start moving with growth factors pointing them in the right direction. Which cells acquire the ability to move depends on the actions of cytokines.
"Each of these signals must work together in order for the cells to proceed to their correct destination. But they are not the only ones," continued Prof Montell.
"We found that [the gene] Par-1 regulates the detachment of cells from the epithelium and a critical step in releasing the cells from the original tissue."
The findings may provide a base from which drug developers can design new therapies to treat ovarian cancer.
