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人类黑色素瘤发起细胞表达神经神经生长因子受体CD271

Alexander D Boiko¹, Olga V Razorenova, Matt van de Rijn

¹Institute for Stem Cell Biology and Regenerative Medicine, Stanford Cancer Center, Stanford University School of Medicine, Stanford, California 94304-5542, USA. aboiko@stanford.edu

|July 3, 2010

概括

黑色素瘤瘤干细胞 (MTSCs) 可以被分离为CD271(+) 细胞. 这些CD271(+) 细胞启动黑色素瘤瘤,并可以转移,解释了有限的T细胞治疗疗效.

科学领域:

在瘤学瘤学.
癌症干细胞生物学
免疫学免疫学免疫学

背景情况:

人类黑色素瘤中瘤致癌干细胞的存在是最近的一个研究领域.
了解黑色素瘤瘤干细胞 (MTSC) 对于开发有效的癌症疗法至关重要.

研究的目的:

在人类黑色素瘤中对瘤致癌干细胞进行前性分离和鉴定.
研究已识别的黑色素瘤细胞群的瘤发起能力和转移潜力.

主要方法:

使用光激活细胞分类 (FACS) 进行CD271(+) 黑色素瘤细胞的潜在分离.
将分离的细胞移植到免疫缺陷小鼠 (Rag2(-/-) gammac(-/-)) 中,植入人体皮肤或骨.
在体内瘤形成和转移的评估.
分析CD271瘤细胞上的抗原表达 (TYR,MART1,MAGE).

主要成果:

一个高度丰富的CD271(+) MTSC群体被成功分离出来,最大限度地实现了可行的细胞移植.
在90%的测试黑色素瘤中,CD271 (((+) 细胞子集是主要的瘤发起人群.
在小鼠中,移植的CD271 (((+) 细胞形成了黑色素瘤,并表现出转移潜力.
CD271 ((+) 黑色素瘤细胞经常缺乏TYR,MART1和MAGE抗原的表达.

结论:

CD271(+) 细胞代表了人类黑色素瘤中瘤致癌干细胞.
鉴定到的MTSC群体发病和转移瘤的能力对黑色素瘤治疗有重大影响.
在CD271 (((+) 细胞上缺乏特定抗原表达可能解释了针对这些抗原的T细胞疗法的有限疗效.

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