美國科學(xué)家在4月3日出版的《細(xì)胞·干細(xì)胞》雜志上發(fā)表論文指出，已長成球體的老鼠皮膚細(xì)胞，即便沒有干細(xì)胞基因的基因操縱，仍可導(dǎo)致具有癌癥干細(xì)胞特性的細(xì)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(xì)胞產(chǎn)生癌癥干細(xì)胞的潛在途徑，*終甚至可研究出一種更**的策略，以制造用于再生**的iPS細(xì)胞（誘導(dǎo)多能干細(xì)胞）。

美國路易斯維爾大學(xué)健康科學(xué)中心的道格拉斯#8226;戴恩博士表示，所有固態(tài)腫瘤的一個(gè)標(biāo)志是癌癥細(xì)胞過度生長成三維結(jié)構(gòu)。研究人員對異常的細(xì)胞結(jié)構(gòu)是否會(huì)觸發(fā)已分化細(xì)胞重組為類似于癌癥干細(xì)胞的細(xì)胞進(jìn)行了研究。

研究人員發(fā)現(xiàn)，所有視網(wǎng)膜母細(xì)胞瘤腫瘤抑制基因（RB1）家族成員的突變，可導(dǎo)致細(xì)胞過度生長形成球體，從而觸發(fā)類似癌癥干細(xì)胞的細(xì)胞產(chǎn)生，而RB1對于調(diào)控細(xì)胞接觸抑制及限制正常細(xì)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(xì)胞可表達(dá)出胚胎干細(xì)胞中所表達(dá)出來的關(guān)鍵基因，并引起不同的已分化細(xì)胞。

有趣的是，只有一個(gè)RB1突變的細(xì)胞仍保持接觸抑制，但是將其從培養(yǎng)皿以機(jī)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(xì)胞的特征。即使RB1基因完好無損的細(xì)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(xì)胞，一旦注入老鼠體內(nèi)并分化成早期癌癥的突變細(xì)胞時(shí)，就會(huì)形成腫瘤。

研究人員推測，在動(dòng)物身上，癌癥干細(xì)胞也許是作為過度生長細(xì)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(xì)胞基因自發(fā)地在已分化細(xì)胞中被再次激活的**個(gè)例子。研究人員提出，當(dāng)RB1路徑受到抑制時(shí)，細(xì)胞接觸抑制的喪失會(huì)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(xì)胞重組為具有癌癥干細(xì)胞特性的細(xì)胞。（創(chuàng)賽技術(shù)中心 canspecsci.com）

推薦原始出處：

Cell Stem Cell, 3 April2009doi:10.1016/j.stem.2009.02.015

Mouse Fibroblasts Lacking RB1FunctionForm Spheres and Undergo Reprogramming to a Cancer StemCellPhenotype

Yongqing Liu1,2,Brian Clem1,EwaK.Zuba-Surma3,Shahenda El-Naggar1,2,Sucheta Telang1,AlfredB.Jenson1,Yali Wang2,Hui Shao2,Mariusz Z.Ratajczak3,JasonChesney1andDouglas C. Dean1,2,4,,

1 Molecular Targets Program, Brown Cancer Center, UniversityofLouisville Health Sciences Center, Louisville, KY 40202, USA
2 Department of Ophthalmology and Visual Sciences, UniversityofLouisville Health Sciences Center, Louisville, KY 40202, USA
3 Stem Cell Biology Program, Brown Cancer Center, UniversityofLouisville Health Sciences Center, Louisville, KY 40202, USA
4 Department of Biochemistry and Molecular Biology, UniversityofLouisville Health Sciences Center, Louisville, KY 40202, USA

Summary

Activation of the RB1 pathway triggers the cell-cycle arrestthatmediates cell-cell contact inhibition. Accordingly, mutationof allthree RB1 family members leads to loss of contact inhibitionandoutgrowth offibroblasts into spheres where cell-cellcontactspredominate. We present evidence that such outgrowthtriggersreprogramming to generate cells with properties of cancerstemcells. Fibroblasts with only a single RB1 mutation remaincontactinhibited; however, if this contact inhibition is bypassedbyforcing the RB1/ cells to form spheres in suspension, cellswithproperties of cancer stem cells are also generated. These cellsnotonly form tumors in nude mice but also generatedifferentiatedcells. We propose that contact inhibition imposed bythe RB1pathway performs an unexpected tumor suppressor functionbypreventing cell outgrowth into structures where cellswithproperties of cancer stem cells can be generatedfromdifferentiated somatic cells in advancingcancers.