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不平等的癌细胞:后勤部队与探路先锋相呼应(附原文) [复制链接]

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楼主
发表于 2012-5-18 18:19 |只看该作者 |倒序浏览 |打印
本帖最后由 细胞海洋 于 2012-5-20 23:23 编辑 9 R0 ?7 K; S8 A

) x& O9 U8 y; M1 j+ v2 Q: s- p7 \All Cancer Cells Are Not Created Equal: Some Cell Types Control Continued Tumor Growth, Others Prepare the Way for Metastasis' {3 d6 g" m! ^  }
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ScienceDaily (May 15, 2012) — A study from Massachusetts General Hospital (MGH) researchers suggests that specific populations of tumor cells have different roles in the process by which tumors make new copies of themselves and grow. In their report in the May 15 issue of Cancer Cell, researchers identify a tumor-propagating cell required for the growth of a pediatric muscle tumor in a zebrafish model and also show that another, more-differentiated tumor cell must first travel to sites of new tumor growth to prepare an environment that supports metastatic growth.
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"Most investigators have thought that tumor-propagating cells -- what are sometimes called cancer stem cells -- must be the first colonizing cells that travel from the primary tumor to start the process of local invasion and metastasis, but in this model, this is simply not the case," says David Langenau, PhD, of the MGH Department of Pathology and Center for Cancer Research, who led the study. "Instead, the colonizing cells lack the ability to divide and instead prime newly infiltrated regions for the eventual recruitment of slow-moving cancer stem cells. It will be important to test how broadly this phenomenon is found in a diversity of animal and human cancers.": W' m" z; I$ R5 c+ o! I' h
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Langenau's team has long been using zebrafish to study rhabdomyosarcoma (RMS), an aggressive pediatric cancer. In embryonic zebrafish, RMS can develop within 10 days, and since the tiny fish are transparent at that stage, fluorescent markers attached to particular cellular proteins can easily be imaged. The current study used these properties to monitor how specific populations of tumor cells develop and their role in initiating new tumor growth.
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1 e* A) Y/ i. `# ?. {2 A/ {Previous research from the MGH team had discovered that RMS cells expressing marker proteins also seen on muscle progenitor cells had significantly more tumor-propagating potential than did other tumor cells. Fluorescently labeling proteins associated with different stages of cellular differentiation revealed distinct populations of RMS cells in the zebrafish model. Cells expressing the progenitor cell marker myf5, were labeled green, and those expressing myogenin, a marker of mature muscle cells, were labeled red.
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9 w. k; d1 |  g) f; d* R  AIn a series of experiments, the research team confirmed that myf5-expressing RMS cells had powerful tumor-propagating potential, but the ability to visualize how tumor cells move in living fish produced a surprising observation. While myf5-expressing cells largely remained within the primary tumor itself, myogenin-expressing RMS cells easily moved out from the tumor, entering the vascular system and passing through usually impenetrable layers of collagen. Only after the more-differentiated but non-proliferative myogenin-expressing cells had colonized an area did the myf5-expressing tumor-propagating cells appear and start the growth a new tumor. Imaging the labeled tumor cells also revealed that different cellular populations tended to cluster in different areas of later-stage tumors.9 d4 i3 A( q  x, i2 G; e
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"Our direct in-vivo imaging studies are the first to suggest such diverse cellular functions in solid tumors, based on differentiation and the propensity for self-renewal," says Myron Ignatius, PhD, of MGH Pathology and Center for Cancer Research, the study's first author. "I think we will find that this kind of division of labor is a common theme in cancer, especially given that the vast majority of cells within a tumor are not tumor-propagating cells. We suspect there will be molecularly defined populations that make niches for tumor-propagating cells, secrete factors to recruit vasculature and create boundaries to suppress immune cell invasion."
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! Z. f9 [3 {2 t8 h* X' uLangenau adds, "Division of labor is a new and emerging concept in cancer research that we hope will lead to new targets for rationally designed therapies. In rhabdomyosarcoma it will be important to target both the tumor-propagating cells and the highly migratory colonizing cells for destruction -- a major focus of ongoing studies in our group." Langenau is an assistant professor of Genetics at Harvard Medical School and a principal faculty member at the Harvard Stem Cell Institute.
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" k! v* l0 \* ^6 DAdditional co-authors author of the Cancer Cell article are Eleanor Chen, Adam Fuller, Ines Tenente Rayn Clagg, Sali Liu, Jessica Blackburn, MGH Pathology and Center for Cancer Research; Andrew Rosenberg, and Petur Neilsen, MGH Pathology; Natalie Elpek and Thorsten Mempel, MGH Center for Immunology and Inflammatory Diseases; and Corinne Linardic, Duke University Medical Center. The study was supported by grants from the National Institute of Health, the Alex's Lemonade Stand Foundation, the Sarcoma Foundation of America, the American Cancer Society and the Harvard Stem Cell Institute.5 I4 d) j$ y  B, R- p
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4楼原文 感谢naturalkillerce 提供http://www.sciencedaily.com/releases/2012/05/120515131756.htm' e+ O2 v9 G7 P% O# l
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沙发
发表于 2012-5-18 22:50 |只看该作者
有道理,有新意。求原文。还想请楼主谈谈您自己对该工作的想法。谢谢!

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发表于 2012-5-19 15:57 |只看该作者
回复 sunsong7 的帖子9 O2 e1 Y) Y. U7 }" S- h, `! D* L

0 d" h; y% m! Y. g4 ^, S利用活体成像技术揭示肿瘤细胞异质性4 q3 j& K$ P1 m, }# d' u
时间:2012-05-17 08:28:52 来源:生物无忧 作者:davidtower" O) Z# L4 l7 D6 {
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美国麻省总医院(Massachusetts General Hospital, MGH)研究人员开展的一项新研究表明,肿瘤细胞的特定群体在肿瘤自我增殖和成长的过程中发挥着不同的作用.在这项研究中,研究人员在斑马鱼模式动物中,鉴定出一种肿瘤扩散细胞(tumor-propagating cell)是小儿肌肉肿瘤(pediatric muscle tumor)生长所必需的,而且也表明另一种更加分化的肿瘤细胞必须先前往新肿瘤生长的地方以便准备好支持转移瘤生长的环境.相关研究结果于2012年5月15日发表在Cancer Cell期刊上,论文标题为"In Vivo Imaging of Tumor-Propagating Cells, Regional Tumor Heterogeneity, and Dynamic Cell Movements in Embryonal Rhabdomyosarcoma".
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"大多数研究者认为,肿瘤扩散细胞---有时也被称为癌干细胞(cancer stem cell)---必须是第一批离开原发性肿瘤而开启局部浸润和转移过程的定植细胞(colonizing cell),但在这种模式动物中,实际情形根本不是如此",论文通讯作者和麻省总医院病理科与癌症研究中心研究员David Langenau博士说,"相反,定植细胞缺乏分裂的能力,并且准备好新浸润的区域以便最终招募缓慢移动的癌干细胞.因此,测试这种现象在各种各样的动物和人类癌症中如何广泛存在,将是比较重要的."
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1 j% `( b' L! p' }6 u* c    Langenau领导的研究小组长期以来一直使用斑马鱼来研究一种侵袭性的小儿癌症,即横纹肌肉瘤(rhabdomyosarcoma, RMS).在斑马鱼胚胎中,RMS能够在10天内产生,而且因为斑马鱼在这个阶段是透明的,所以研究人员能够很容易利用附着到特定细胞蛋白质上的荧光标记进行成像.在当前的研究中,他们利用这些属性来监测特定肿瘤细胞群体在启动新肿瘤生长中是如何发挥作用的." b4 O8 H' ?- b0 P6 x

7 j! N6 M8 i/ K4 n# _* g    Langenau领导的研究小组在之前的研究中发现,他们在肌祖细胞(muscle progenitor cell)中也观察到表达标记蛋白的RMS细胞,而且这种RMS细胞要比其他肿瘤细胞有着显著性更高的肿瘤扩散潜力.与细胞分化不同阶段相关联的荧光标记蛋白揭示斑马鱼模式动物中存在截然不同的RMS细胞群体.表达祖细胞标记物myf5的细胞用绿色荧光标记,而表达成熟肌细胞标记物肌细胞生成素(myogenin)的那些细胞用红色荧光标记.$ j; r9 |1 b7 U( ~* M

% C  }. j3 P, {+ @% z    在一系列的实验中,研究小组证实表达myf5的RMS细胞有着强大的肿瘤扩散潜力,但是,研究人员在能够可视化观察肿瘤细胞在活的斑马鱼体内如何移动的过程中,获得令人吃惊的发现.尽管表达myf5的RMS细胞主要保留在原发性肿瘤中,但是表达肌细胞生成素的RMS细胞很容易离开原发性肿瘤,进入血液系统,并穿过通常难以穿越的胶原蛋白层.只有那些更加分化的但非增殖性的表达肌细胞生成素的细胞在一个区域定植之后,表达myf5的肿瘤扩散细胞然后才能出现这种区域,并开启新肿瘤生长.对标记的肿瘤细胞进行成像也揭示不同的细胞群体倾向于簇集在晚期肿瘤中的不同区域.# r1 e7 q, P7 W$ T

6 Z1 o# F5 I5 |- j1 F; D8 F    论文第一作者和麻省总医院病理科与癌症研究中心研究员Myron Ignatius博士说,"基于肿瘤细胞的分化和自我更新性质,我们的直接活体成像研究是第一次提示着实体肿瘤中存在如此多样化的细胞功能.我认为我们将会发现,这种分工是癌症中常见的现象,特别是考虑到肿瘤内绝大多数细胞并不是肿瘤扩散细胞.我们猜测将存在分子界定的肿瘤细胞群体为肿瘤扩散细胞构建微环境,并分泌一些因子来招募血管组分,创造抑制免疫细胞入侵的边界."5 x) Z+ `; N+ d  z+ ~: O! Z$ B5 u: T
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    Langenau 补充道,"分工在癌症研究中是一种新兴的概念.我们希望通过研究分工将能够导致我们发现新靶标用于合理设计疗法.在横纹肌肉瘤中,靶向摧毁肿瘤扩散细胞和高度移动性的定植细胞将是非常重要的,这也是我们的研究小组正在进行的研究的一个主要重点."0 w# l: c$ f+ [
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发表于 2012-5-19 17:52 |只看该作者
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