美国科学家在4月3日出版的《细胞·干细胞》杂志上发表论文指出，已长成球体的老鼠皮肤细胞，即便没有干细胞基因的基因操纵，仍可导致具有癌症干细胞特性的细胞产生。此一意想不到的发现，提供了一种从已分化细胞产生癌症干细胞的潜在途径，最终甚至可研究出一种更安全的策略，以制造用于再生治疗的iPS细胞（诱导多能干细胞）。
美国路易斯维尔大学健康科学中心的道格拉斯•戴恩博士表示，所有固态肿瘤的一个标志是癌症细胞过度生长成三维结构。研究人员对异常的细胞结构是否会触发已分化细胞重组为类似于癌症干细胞的细胞进行了研究。
研究人员发现，所有视网膜母细胞瘤肿瘤抑制基因（RB1）家族成员的突变，可导致细胞过度生长形成球体，从而触发类似癌症干细胞的细胞产生，而RB1对于调控细胞接触抑制及限制正常细胞长成如肿瘤般的三维结构至关紧要。令人惊讶的是，这种类癌症干细胞可表达出胚胎干细胞中所表达出来的关键基因，并引起不同的已分化细胞。
有趣的是，只有一个RB1突变的细胞仍保持接触抑制，但是将其从培养皿以机械方式分离并迫使其形成球体后，它们也可表现出类似于癌症干细胞的特征。即使RB1基因完好无损的细胞都能被迫形成球体，这说明RB1的缺失对重组来说并不是必需的。研究人员还发现，从RB1被破坏的球体分离出来的类癌症干细胞，一旦注入老鼠体内并分化成早期癌症的突变细胞时，就会形成肿瘤。
研究人员推测，在动物身上，癌症干细胞也许是作为过度生长细胞的某种直接功能而产生的，这是静默的内源性胚胎干细胞基因自发地在已分化细胞中被再次激活的第一个例子。研究人员提出，当RB1路径受到抑制时，细胞接触抑制的丧失会导致其过度生长成球状结构，早期癌症中的此种情况可触发已分化细胞重组为具有癌症干细胞特性的细胞。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
