Science:前列腺癌的细胞起源

来源:EurekAlert! 发布时间:2010年07月30日 浏览次数: 【字体: 收藏 打印文章

癌症干细胞假说提出,在一个肿瘤中,只有小部分的细胞能够启动肿瘤的生长。这一假说激发了寻找产生人类常见上皮性肿瘤的细胞的兴趣。 就前列腺癌这种情况而言,研究人员认为,管腔细胞是该种癌症的细胞起源。但有关这一理论的证据主要是根据人类肿瘤的组织学研究或是对来自小鼠组织的肿瘤的研究。

Andrew Goldstein及其同事使用了一种新的功能性检验方法:他们从人类的良性前列腺组织中分离出了基底细胞和管腔细胞,并用肿瘤基因转变它们,然后再将这些细胞移植到小鼠体内。 他们的结果表明,基底细胞而非管腔细胞产生了与在人体中所见的前列腺肿瘤非常接近的前列腺肿瘤;研究人员提醒道,当在确定人类癌症的细胞起源时仅仅根据组织学的研究可能会产生误导。

原文出处:

Science DOI: 10.1126/science.1189992

Identification of a Cell of Origin for Human Prostate Cancer
Andrew S. Goldstein,1 Jiaoti Huang,2,3,6 Changyong Guo,2,4 Isla P. Garraway,2,4 Owen N. Witte1,5,6,*

Luminal cells are believed to be the cells of origin for human prostate cancer, because the disease is characterized by luminal cell expansion and the absence of basal cells. Yet functional studies addressing the origin of human prostate cancer have not previously been reported because of a lack of relevant in vivo human models. Here we show that basal cells from primary benign human prostate tissue can initiate prostate cancer in immunodeficient mice. The cooperative effects of AKT, ERG, and androgen receptor in basal cells recapitulated the histological and molecular features of human prostate cancer, with loss of basal cells and expansion of luminal cells expressing prostate-specific antigen and alpha-methylacyl-CoA racemase. Our results demonstrate that histological characterization of cancers does not necessarily correlate with the cellular origins of the disease.

1 Molecular Biology Institute, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA.
2 Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA 90095, USA.
3 Department of Pathology and Laboratory Medicine, UCLA, Los Angeles, CA 90095, USA.
4 Department of Urology, UCLA, Los Angeles, CA 90095, USA.
5 Department of Microbiology, Immunology and Molecular Genetics; Department of Molecular and Medical Pharmacology; Howard Hughes Medical Institute, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095, USA.
6 Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, UCLA, Los Angeles, CA 90095, USA.

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