腫瘤干細(xì)胞可啟動(dòng)小鼠的腫瘤產(chǎn)生

1、腫瘤干細(xì)胞可啟動(dòng)小鼠的腫瘤產(chǎn)生生物谷 熱點(diǎn)推薦熱點(diǎn)推薦生生物物谷谷盤盤點(diǎn)點(diǎn)2 20 00 09 92009 年，國內(nèi)生物醫(yī)藥的突破之年。不僅有干細(xì)胞發(fā)現(xiàn)的新突破，還有轉(zhuǎn)基因作物政策的新舉措。更多專題相關(guān)閱讀相關(guān)閱讀推推薦薦學(xué)學(xué)術(shù)術(shù)會(huì)會(huì)議議 學(xué)術(shù)研討會(huì)、峰會(huì)論壇、展會(huì)更多會(huì)議 生物谷報(bào)道：干細(xì)胞是體內(nèi)可以發(fā)育為機(jī)體的血液或組織的主細(xì)胞，近來兩個(gè)不同的研究小組周日發(fā)表文章認(rèn)為干細(xì)胞可能會(huì)導(dǎo)致腫瘤。 加拿大和意大利的研究者發(fā)現(xiàn)小鼠的特定腸癌干細(xì)胞是腸癌發(fā)生的來源。他們的發(fā)現(xiàn)發(fā)表在自然雜志上，表明腫瘤干細(xì)胞將成為癌癥治療的靶標(biāo)。同樣結(jié)果也發(fā)現(xiàn)于淋巴瘤、乳腺癌和腦腫瘤，但是兩個(gè)研究小組是首次發(fā)現(xiàn)腫瘤干細(xì)

2、胞可導(dǎo)致腸癌。他們采用腫瘤研究的常用方法，即將人腸癌細(xì)胞移植進(jìn)入免疫缺陷的小鼠體內(nèi)。只有表面含有 CD133 蛋白的特定細(xì)胞才能產(chǎn)生新的腫瘤。CD133 首先在腦瘤和前列腺癌中被發(fā)現(xiàn)。隨后羅馬的意大利高級衛(wèi)生研究院的Ruggero De Maria 及其同事將 CD133 細(xì)胞注入免疫缺陷小鼠皮膚內(nèi)可以產(chǎn)生腫瘤。在自然的一篇專論認(rèn)為這些研究證明與構(gòu)成腫瘤的細(xì)胞不同的一小部分腸癌細(xì)胞可起始腫瘤的生長。腸癌是全球第四大致死性腫瘤，國際衛(wèi)生組織統(tǒng)計(jì)每年有 65.5 萬人死于腸癌。多倫多大學(xué)健康網(wǎng)的 John Dick 及其同事在報(bào)告中寫道，腸癌是從遺傳基因角度已經(jīng)有了清晰認(rèn)識(shí)的一種腫瘤，在加拿大腫瘤

3、相關(guān)死亡中占第二位，表明目前的治療方法不能完全清除腫瘤細(xì)胞。研究者認(rèn)為此研究可設(shè)計(jì)研制特異針對腫瘤干細(xì)胞的藥物，這些藥物可有效的治療腸癌而對正常細(xì)胞無影響。FIGURE 1. Xenografts generated from both bulk and CD133+ colon cancer cells resemble the original patient tumour.The parent tumour (tumour 14) is compared with xenografts generated from both primary and secondary passages

4、of the tumour. The initial passage represents a xenograft generated from the injection of 1 105 bulk human colon cancer cells. The secondary xenograft was generated from the injection of 500 CD133+ colon cancer cells. The histology of the three tumours, as expressed by H&E (haematoxylin and eosi

5、n) staining, shows well to moderately differentiated mucinous adenocarcinomas with intestinal differentiation including numerous goblet cells and intraluminal mucin. The immunohistochemical markers (including CK-20, CK7, CEA, Muc2, MIB-1 and p53) reveal comparable staining patterns in both the bulk

6、and CD133+ xenografts, as compared to the parent tumour. Images for each stain are taken at the same magnification. Scale bar represents 50 m for H&E and 20 m for all other stains.作者簡介作者簡介：John E Dick, PhDSenior ScientistDivision of Cellular & Molecular BiologyToronto General Research Instit

7、ute (TGRI)Keywords: leukemia, stem cells, NOD/SCID mouse Research InterestsSCID mouse an important tool Dr. Dicks research program aims at understanding how stem cells can be manipulated. He is known around the world for his development of an in vivo repopulation assay (ie: in vivo stem cell assay)

8、using the NOD/SCID mouse. HSCs are found in the bone marrow and are pluripotent: they give rise to all the cellular elements of the blood. Until the development of this model, studies of the human hematopoietic system and diseases of the blood were limited because there was no method to study the de

9、velopment of the human blood system. This model has transformed the study of both normal and leukemic human blood systems. The assay involves reconstituting immune deficient SCID mice with either normal human bone marrow or cord blood, or with cells from patients with genetic deficiencies or leukemi

10、a. The mouse, being immune deficient, cannot reject the human cells, and thus the human cells readily proliferate and differentiate, generating human hematopoietic cells of erythroid, lymphoid and myeloid lineage in the mouse. Inside a black box of cancer development Although it is now important wor

11、ldwide as a tool for blood research, the mouse model was initially developed to understand and define both normal and leukemic stem cells. In acute myeloid leukemia, only leukemic stem cells can initiate the disease and we have little understanding of which normal cells become transformed in the ini

12、tiation of leukemia. That iswhy it is important to characterize the developmental programs of both cell types. Without an understanding of how they are different, the mechanism by which the leukemic process alters the development of the normal blood system will never be understood. Effective anti-le

13、ukemia therapy must target the leukemic stem cell to completely eradicate the disease. Using the mouse model, it is possible to identify and characterize the leukemic stem cell and determine where it comes from. Until now, this process has always been a mystery. With this model, we will now be able

14、to see inside that black box, and gain a more complete understanding regarding how the molecular pathways differ in normal and leukemic blood systems. Then we will be able to devise therapies to disrupt the molecular process that leads to leukemia and hopefully prevent it from occurring. Additional Appointments Professor, Medical Genetics and Microbiology, University of Toronto Canada