Nature：肿瘤干细胞可启动小鼠的肿瘤产生
生物谷报道：干细胞是体内可以发育为机体的血液或组织的主细胞，近来两个不同的研究小组周日发表文章认为干细胞可能会导致肿瘤。
加拿大和意大利的研究者发现小鼠的特定肠癌干细胞是肠癌发生的来源。他们的发现发表在《自然》杂志上，表明肿瘤干细胞将成为癌症治疗的靶标。同样结果也发现于淋巴瘤、乳腺癌和脑肿瘤，但是两个研究小组是首次发现肿瘤干细胞可导致肠癌。他们采用肿瘤研究的常用方法，即将人肠癌细胞移植进入免疫缺陷的小鼠体内。只有表面含有CD133蛋白的特定细胞才能产生新的肿瘤。CD133首先在脑瘤和前列腺癌中被发现。随后罗马的意大利高级卫生研究院的Ruggero De Maria及其同事将CD133细胞注入免疫缺陷小鼠皮肤内可以产生肿瘤。在《自然》的一篇专论认为这些研究证明与构成肿瘤的细胞不同的一小部分肠癌细胞可起始肿瘤的生长。
肠癌是全球第四大致死性肿瘤，国际卫生组织统计每年有65.5万人死于肠癌。多伦多大学健康网的John Dick及其同事在报告中写道，肠癌是从遗传基因角度已经有了清晰认识的一种肿瘤，在加拿大肿瘤相关死亡中占第二位，表明目前的治疗方法不能完全清除肿瘤细胞。研究者认为此研究可设计研制特异针对肿瘤干细胞的药物，这些药物可有效的治疗肠癌而对正常细胞无影响。
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 of the tumour. The initial passage represents a xenograft generated from the injection of 1
作者简介：
John E Dick, PhD
Senior Scientist
Division of Cellular & Molecular Biology
Toronto General Research Institute (TGRI)
Keywords: leukemia, stem cells, NOD/SCID mouse
Research Interests
SCID mouse an important tool
Dr. Dick's 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) 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 development 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 leukemia. 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 worldwide 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 initiation of leukemia. That is
why 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-leukemia 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 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,
Pubmed Publications
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Related Webpages
Genome Canada Project: Mass spectrometer-based flow cytometer, methods and applications
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