美國路易斯維爾大學健康科學中心的道格拉斯#8226;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構。研究人員對異常的細胞結構是否會觸發(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構至關緊要。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**個例子。研究人員提出，當RB1路徑受到抑制時，細胞接觸抑制的喪失會導致其過度生長成球狀結構，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。（創(chuàng)賽技術中心 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.