《Nature》癌症溯源 元凶干细胞

　　

生物通报道，哥伦比亚大学Herbert Irving癌症综合研究中心，病理系，细胞生物学系，医学系，遗传与发育系等多位科学家在Nature在线版上发表癌症干细胞相关研究成果，A luminal epithelial stem cell that is a cell of origin for prostate cancer，找到一种与癌症发生有关的干细胞。

 

文章通讯作者是来自哥伦比亚大学的Michael M. Shen教授，早年在剑桥大学获得博士学位，在哈佛大学接受博士后学位训练，现任哥伦比亚大学正教授，在前列腺癌研究方面颇有建树，今年2月曾在Nature发表前列腺癌相关文章（Diagnostics: The prostate-cancer metabolome，NATURE 457 (7231):799-800 Feb 12 2009）

 

研究人员发现一种表达Nkx3-1基因的上皮干细胞在前列腺癌发生的过程中起重要作用，这类细胞被命名为：CARNs （castration-resistant Nkx3-1-expressing cells），CARNs具有自我更新能力，并具有重新发育为前列腺管的能力。

 

这些结果表明，Nkx3-1突变的细胞是产生前列腺癌的原因，Nkx3-1基因是维持干细胞性能的基因。CARNs细胞是一类前列腺癌干细胞。

 

尽管这只是一项动物实验，但弄清前列腺中哪些细胞引发癌症有助于开发出更好的前列腺癌疗法。

（生物通 小茜）

09新产品 癌症芯片分析产品

 

生物通推荐原文检索

Nature advance online publication 9 September 2009 | doi:10.1038/nature08361; Received 11 April 2008; Accepted 5 August 2009; Published online 9 September 2009

 

A luminal epithelial stem cell that is a cell of origin for prostate cancer

Xi Wang1,2,5,6, Marianna Kruithof-de Julio1,2, Kyriakos D. Economides5,7,8, David Walker5,6,8, Hailong Yu5,6,8, M. Vivienne Halili5,6,8, Ya-Ping Hu5,6,8, Sandy M. Price5,6, Cory Abate-Shen3,4,5,7 & Michael M. Shen1,2,5,6

 

Department of Medicine,

Department of Genetics and Development,

Department of Urology, and,

Department of Pathology and Cell Biology, Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA

Center for Advanced Biotechnology and Medicine,

Department of Pediatrics, and,

Department of Medicine, UMDNJ–Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA

Present addresses: Department of Biological Sciences, Sanofi-Aventis, Bridgewater, New Jersey 08807, USA (K.D.E.); Department of Molecular Biology, Bristol-Myers Squibb Research Institute, Princeton, New Jersey 08543, USA (D.W.); Department of Food Science, Rutgers University, Piscataway, New Jersey 08901, USA (H.Y.); Cardiovascular Diseases Group, Merck Research Laboratories, Rahway, New Jersey 07065, USA (M.V.H.); Johnson and Johnson Skin Research Center, Skillman, New Jersey 08558, USA (Y.-P.H.); Department of Medical Oncology, Cancer Institute of New Jersey, New Brunswick, New Jersey 08903, USA (S.M.P.).

【Abstract】

In epithelial tissues, the lineage relationship between normal progenitor cells and cell type(s) of origin for cancer has been poorly understood. Here we show that a known regulator of prostate epithelial differentiation, the homeobox gene Nkx3-1, marks a stem cell population that functions during prostate regeneration. Genetic lineage-marking demonstrates that rare luminal cells that express Nkx3-1 in the absence of testicular androgens (castration-resistant Nkx3-1-expressing cells, CARNs) are bipotential and can self-renew in vivo, and single-cell transplantation assays show that CARNs can reconstitute prostate ducts in renal grafts. Functional assays of Nkx3-1 mutant mice in serial prostate regeneration suggest that Nkx3-1 is required for stem cell maintenance. Furthermore, targeted deletion of the Pten tumour suppressor gene in CARNs results in rapid carcinoma formation after androgen-mediated regeneration. These observations indicate that CARNs represent a new luminal stem cell population that is an efficient target for oncogenic transformation in prostate cancer.