美國科學(xué)家在4月3日出版的《細胞·干細胞》雜志上發(fā)表論文指出，已長成球體的老鼠皮膚細胞,，即便沒有干細胞基因的基因操縱，仍可導(dǎo)致具有癌癥干細胞特性的細胞產(chǎn)生,。此一意想不到的發(fā)現(xiàn),，提供了一種從已分化細胞產(chǎn)生癌癥干細胞的潛在途徑，最終甚至可研究出一種更安全的策略,，以制造用于再生治療的iPS細胞（誘導(dǎo)多能干細胞）,。
美國路易斯維爾大學(xué)健康科學(xué)中心的道格拉斯•戴恩博士表示，所有固態(tài)腫瘤的一個標志是癌癥細胞過度生長成三維結(jié)構(gòu),。研究人員對異常的細胞結(jié)構(gòu)是否會觸發(fā)已分化細胞重組為類似于癌癥干細胞的細胞進行了研究,。
研究人員發(fā)現(xiàn)，所有視網(wǎng)膜母細胞瘤腫瘤抑制基因（RB1）家族成員的突變,，可導(dǎo)致細胞過度生長形成球體,，從而觸發(fā)類似癌癥干細胞的細胞產(chǎn)生，而RB1對于調(diào)控細胞接觸抑制及限制正常細胞長成如腫瘤般的三維結(jié)構(gòu)至關(guān)緊要,。令人驚訝的是,，這種類癌癥干細胞可表達出胚胎干細胞中所表達出來的關(guān)鍵基因，并引起不同的已分化細胞,。
有趣的是,，只有一個RB1突變的細胞仍保持接觸抑制，但是將其從培養(yǎng)皿以機械方式分離并迫使其形成球體后,，它們也可表現(xiàn)出類似于癌癥干細胞的特征,。即使RB1基因完好無損的細胞都能被迫形成球體，這說明RB1的缺失對重組來說并不是必需的,。研究人員還發(fā)現(xiàn),，從RB1被破壞的球體分離出來的類癌癥干細胞，一旦注入老鼠體內(nèi)并分化成早期癌癥的突變細胞時,，就會形成腫瘤,。
研究人員推測，在動物身上,，癌癥干細胞也許是作為過度生長細胞的某種直接功能而產(chǎn)生的,，這是靜默的內(nèi)源性胚胎干細胞基因自發(fā)地在已分化細胞中被再次激活的第一個例子。研究人員提出,，當(dāng)RB1路徑受到抑制時,，細胞接觸抑制的喪失會導(dǎo)致其過度生長成球狀結(jié)構(gòu),，早期癌癥中的此種情況可觸發(fā)已分化細胞重組為具有癌癥干細胞特性的細胞。（生物谷Bioon.com）
生物谷推薦原始出處：
Cell Stem Cell, 3 April 2009 doi:10.1016/j.stem.2009.02.015
Mouse Fibroblasts Lacking RB1 Function Form Spheres and Undergo Reprogramming to a Cancer Stem Cell Phenotype
Yongqing Liu1,2,Brian Clem1,Ewa K. Zuba-Surma3,Shahenda El-Naggar1,2,Sucheta Telang1,Alfred B. Jenson1,Yali Wang2,Hui Shao2,Mariusz Z. Ratajczak3,Jason Chesney1andDouglas C. Dean1,2,4,,
1 Molecular Targets Program, Brown Cancer Center, University of Louisville Health Sciences Center, Louisville, KY 40202, USA
2 Department of Ophthalmology and Visual Sciences, University of Louisville Health Sciences Center, Louisville, KY 40202, USA
3 Stem Cell Biology Program, Brown Cancer Center, University of Louisville Health Sciences Center, Louisville, KY 40202, USA
4 Department of Biochemistry and Molecular Biology, University of Louisville Health Sciences Center, Louisville, KY 40202, USA
Summary
Activation of the RB1 pathway triggers the cell-cycle arrest that mediates cell-cell contact inhibition. Accordingly, mutation of all three RB1 family members leads to loss of contact inhibition and outgrowth offibroblasts into spheres where cell-cell contacts predominate. We present evidence that such outgrowth triggers reprogramming to generate cells with properties of cancer stem cells. Fibroblasts with only a single RB1 mutation remain contact inhibited; however, if this contact inhibition is bypassed by forcing the RB1/ cells to form spheres in suspension, cells with properties of cancer stem cells are also generated. These cells not only form tumors in nude mice but also generate differentiated cells. We propose that contact inhibition imposed by the RB1 pathway performs an unexpected tumor suppressor function by preventing cell outgrowth into structures where cells with properties of cancer stem cells can be generated from differentiated somatic cells in advancing cancers.
