生物谷報道：法國居里研究所、以色列Weizmann科學(xué)研究所和德國Technischen大學(xué)的研究人員，合力研究一種名為fascin的蛋白在腸癌擴(kuò)散中所扮演的角色,。
居里研究所Danijela Vignjevic說：“癌細(xì)胞獲得運動和入侵其它組織的能力后開始轉(zhuǎn)移,。與所有能運動的細(xì)胞一樣,，這種新行為依賴于感官細(xì)胞器絲狀偽足（filopodia）感覺環(huán)境,，幫助細(xì)胞決定運動方向。”研究結(jié)果刊登于《Cell Migration》。
“Fascin是絲狀偽足的關(guān)鍵成分,，在腸癌細(xì)胞內(nèi)部,，是導(dǎo)致許多基因活化某回路的靶標(biāo)。”研究人員發(fā)現(xiàn),，在腫瘤發(fā)展的過程中,，fascin的水平也在上升。體外檢測顯示fascin促進(jìn)細(xì)胞遷移和入侵,，體內(nèi)實驗證實fascin與轉(zhuǎn)移有關(guān),。Fascin在細(xì)胞支架的形成過程中發(fā)揮關(guān)鍵作用，因此影響細(xì)胞的運動方式,。研究人員還發(fā)現(xiàn)腫瘤擴(kuò)散到次級位點后,，fascin不再有活性。
Vignjevic與其同事打算制作一個腸癌轉(zhuǎn)移的轉(zhuǎn)基因小鼠模型,，以獲得更多信息,。一位研究人員強調(diào)卵巢癌只有在特定信號刺激下才開始遷移。約翰霍普金斯大學(xué)Denise Montell教授解釋說表皮卵巢癌出現(xiàn)在卵巢特別是覆蓋卵巢外表面的細(xì)胞,，控制這些細(xì)胞的機制與控制腫瘤細(xì)胞的機制類似,。表皮細(xì)胞的遷移方式與癌細(xì)胞的遷移方式類似，并且這種運動與細(xì)胞對周圍環(huán)境的信號的反應(yīng)高度協(xié)調(diào)一致,。利用小鼠模型,，研究人員鑒別出三種信號。甾類激素決定細(xì)胞開始遷移的時間,，生長因子決定細(xì)胞遷移的方向,，細(xì)胞運動的能力離不開細(xì)胞因子的運動。Montell教授說：“每種信號都要相互協(xié)作,，才能使細(xì)胞朝正確方向移動。但它們并不是唯一的,。我們發(fā)現(xiàn)Par-1基因調(diào)節(jié)細(xì)胞與表皮的分離,，以及原始組織釋放細(xì)胞的一個關(guān)鍵步驟。”這項發(fā)現(xiàn)為藥物制造商設(shè)計治療卵巢癌的新藥提供了參考,。
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.
