生物谷報(bào)道：癌癥干細(xì)胞已經(jīng)從若干人類腫瘤中被分離了出來,。最新發(fā)現(xiàn)的是人類惡性黑素瘤引發(fā)細(xì)胞的一個(gè)亞組,，科學(xué)家根據(jù)它們對(duì)化學(xué)抵抗力調(diào)節(jié)因子ABCB5的表達(dá)將其識(shí)別出來,。ABCB5+亞組的大小與黑素瘤患者臨床病情發(fā)展相關(guān),，初步證據(jù)還表明,，這些黑素瘤干細(xì)胞可以用針對(duì)ABCB5的抗體將其作為特異性目標(biāo),。這為黑素瘤提供了一個(gè)潛在的治療策略,，而且對(duì)這種類型細(xì)胞進(jìn)行研究還有可能回答癌癥生物學(xué)中的重要問題,。本期封面所示混合型黑素瘤細(xì)胞（電腦增強(qiáng)的熒光顯微鏡圖像合成圖）是在活體中所發(fā)生的一次人類腫瘤異種移植中形成的，即通過一個(gè)ABCB5+黑素瘤干細(xì)胞與一種更為分化的ABCB5-腫瘤細(xì)胞融合形成,。細(xì)胞核分別用基因編碼的紅色（DsRed）和綠色（EYFP）熒光標(biāo)簽作了標(biāo)記,。
生物谷推薦英文原文：
Nature 451, 345-349 (17 January 2008) | doi:10.1038/nature06489; Received 13 June 2007; Accepted 21 November 2007
Identification of cells initiating human melanomas
Tobias Schatton1, George F. Murphy2, Natasha Y. Frank1,3, Kazuhiro Yamaura1, Ana Maria Waaga-Gasser4, Martin Gasser4, Qian Zhan2, Stefan Jordan1, Lyn M. Duncan5, Carsten Weishaupt6, Robert C. Fuhlbrigge6, Thomas S. Kupper6, Mohamed H. Sayegh1 & Markus H. Frank1
Transplantation Research Center, Children's Hospital Boston and Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
Department of Pathology and,
Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
Department of Surgery, University of Würzburg Medical School, 97080 Würzburg, Germany
Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA
Harvard Skin Disease Research Center, Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA
Correspondence to: Markus H. Frank1 Correspondence and requests for materials should be addressed to M.H.F. (Email: [email protected]).
Abstract
Tumour-initiating cells capable of self-renewal and differentiation, which are responsible for tumour growth, have been identified in human haematological malignancies1, 2 and solid cancers3, 4, 5, 6. If such minority populations are associated with tumour progression in human patients, specific targeting of tumour-initiating cells could be a strategy to eradicate cancers currently resistant to systemic therapy. Here we identify a subpopulation enriched for human malignant-melanoma-initiating cells (MMIC) defined by expression of the chemoresistance mediator ABCB5 (refs 7, 8) and show that specific targeting of this tumorigenic minority population inhibits tumour growth. ABCB5+ tumour cells detected in human melanoma patients show a primitive molecular phenotype and correlate with clinical melanoma progression. In serial human-to-mouse xenotransplantation experiments, ABCB5+ melanoma cells possess greater tumorigenic capacity than ABCB5- bulk populations and re-establish clinical tumour heterogeneity. In vivo genetic lineage tracking demonstrates a specific capacity of ABCB5+ subpopulations for self-renewal and differentiation, because ABCB5+ cancer cells generate both ABCB5+ and ABCB5- progeny, whereas ABCB5- tumour populations give rise, at lower rates, exclusively to ABCB5- cells. In an initial proof-of-principle analysis, designed to test the hypothesis that MMIC are also required for growth of established tumours, systemic administration of a monoclonal antibody directed at ABCB5, shown to be capable of inducing antibody-dependent cell-mediated cytotoxicity in ABCB5+ MMIC, exerted tumour-inhibitory effects. Identification of tumour-initiating cells with enhanced abundance in more advanced disease but susceptibility to specific targeting through a defining chemoresistance determinant has important implications for cancer therapy.
