人體腫瘤中的癌癥干細(xì)胞,已在功能實(shí)驗(yàn)中被定義為當(dāng)移植進(jìn)免疫缺陷小鼠體內(nèi)時(shí)能形成腫瘤和自我更新的細(xì)胞,。實(shí)驗(yàn)證明,,對(duì)若干腫瘤類(lèi)型來(lái)說(shuō),,這種細(xì)胞相對(duì)較少見(jiàn)。據(jù)此,,研究人員總結(jié)出了一些基于一個(gè)“癌癥干細(xì)胞模型”的治療方法,,該模型正是以這些干細(xì)胞為目標(biāo),而不是以整個(gè)腫瘤或整個(gè)細(xì)胞群為目標(biāo),。
新的研究工作表明,,至少對(duì)人體黑素瘤來(lái)說(shuō),癌癥干細(xì)胞模型可能并不適用,。腫瘤形成潛力是黑素瘤細(xì)胞的一個(gè)共性,。在這些實(shí)驗(yàn)中,研究人員從12位患者身上取來(lái)黑素瘤細(xì)胞,,并進(jìn)行異種移植分析,,發(fā)現(xiàn)約四分之一的黑素瘤細(xì)胞可在小鼠身上形成腫瘤。這表明,,一系列不同癌癥細(xì)胞都有幫助腫瘤發(fā)展的潛力,,從而也向?qū)iT(mén)針對(duì)“癌癥干細(xì)胞”這一小細(xì)胞群的治療方法提出了質(zhì)疑。本期封面圖片所示為黑素瘤細(xì)胞及從這種細(xì)胞形成的腫瘤,。(生物谷Bioon.com)
生物谷推薦原始出處:
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.