人体肿瘤中的癌症干细胞,已在功能实验中被定义为当移植进免疫缺陷小鼠体内时能形成肿瘤和自我更新的细胞。实验证明,对若干肿瘤类型来说,这种细胞相对较少见。据此,研究人员总结出了一些基于一个“癌症干细胞模型”的治疗方法,该模型正是以这些干细胞为目标,而不是以整个肿瘤或整个细胞群为目标。
新的研究工作表明,至少对人体黑素瘤来说,癌症干细胞模型可能并不适用。肿瘤形成潜力是黑素瘤细胞的一个共性。在这些实验中,研究人员从12位患者身上取来黑素瘤细胞,并进行异种移植分析,发现约四分之一的黑素瘤细胞可在小鼠身上形成肿瘤。这表明,一系列不同癌症细胞都有帮助肿瘤发展的潜力,从而也向专门针对“癌症干细胞”这一小细胞群的治疗方法提出了质疑。本期封面图片所示为黑素瘤细胞及从这种细胞形成的肿瘤。(生物谷Bioon.com)
生物谷推荐原始出处:
Nature 456, 593-598 (4 December 2008) | doi:10.1038/nature07567
Efficient tumour formation by single human melanoma cells
Elsa Quintana1,3, Mark Shackleton1,3, Michael S. Sabel, Douglas R. Fullen, Timothy M. Johnson4 & Sean J. Morrison1
1 Howard Hughes Medical Institute, Life Sciences Institute, Department of Internal Medicine, and Center for Stem Cell Biology, University of Michigan, Ann Arbor, Michigan 48109-2216, USA
2 Department of Dermatology, University of Michigan, Ann Arbor, Michigan 48109, USA
3 These authors contributed equally to this work.
A fundamental question in cancer biology is whether cells with tumorigenic potential are common or rare within human cancers. Studies on diverse cancers, including melanoma, have indicated that only rare human cancer cells (0.1–0.0001%) form tumours when transplanted into non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice. However, the extent to which NOD/SCID mice underestimate the frequency of tumorigenic human cancer cells has been uncertain. Here we show that modified xenotransplantation assay conditions, including the use of more highly immunocompromised NOD/SCID interleukin-2 receptor gamma chain null (Il2rg -/-) mice, can increase the detection of tumorigenic melanoma cells by several orders of magnitude. In limiting dilution assays, approximately 25% of unselected melanoma cells from 12 different patients, including cells from primary and metastatic melanomas obtained directly from patients, formed tumours under these more permissive conditions. In single-cell transplants, an average of 27% of unselected melanoma cells from four different patients formed tumours. Modifications to xenotransplantation assays can therefore dramatically increase the detectable frequency of tumorigenic cells, demonstrating that they are common in some human cancers.