誘導(dǎo)多功能干細胞(iPS細胞)能發(fā)育成各種組織和臟器，但醫(yī)學(xué)家擔(dān)心它們發(fā)生癌變,。日本研究人員13日報告說，他們用小鼠iPS細胞培育出了癌癥干細胞，并確認其發(fā)展成癌細胞的過程，這將有助于提高iPS細胞的安全性,。
日本岡山大學(xué)教授妹尾昌治領(lǐng)導(dǎo)的研究小組13日在美國在線科學(xué)刊物《科學(xué)公共圖書館綜合卷》上報告說，他們首先用小鼠細胞培育出iPS細胞,，然后向培養(yǎng)液中添加曾培育過肺癌,、皮膚癌等癌細胞的液體,，4周后將其中未分化的iPS細胞移植到小鼠皮下,。結(jié)果，小鼠全部患上了癌癥,，其部分癌細胞不斷分化,，還有一些癌細胞向肺轉(zhuǎn)移，研究小組由此確認未分化的上述iPS細胞就是癌癥干細胞,。
研究人員同時發(fā)現(xiàn),，在普通培養(yǎng)液中用常規(guī)方法培育的iPS細胞，移植后不會癌變,，但如果與癌細胞一起培養(yǎng),，多數(shù)iPS細胞會死亡。妹尾昌治指出,，少數(shù)iPS細胞癌變也許是受到癌細胞碎片或者其排出的分泌物影響,。
研究小組認為，如果能更深入地了解iPS細胞癌變過程及其發(fā)展成的癌細胞特點,，將有助于預(yù)防和治療癌癥,。由于癌癥干細胞在腫瘤細胞中所占比例只有百分之幾，采集非常困難,，利用iPS細胞培養(yǎng)成的癌癥干細胞可供制藥企業(yè)開發(fā)新藥,。(生物谷：Bioon.com)
doi:10.1371/journal.pone.0033544
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A Model of Cancer Stem Cells Derived from Mouse Induced Pluripotent Stem Cells
Ling Chen1,2,3, Tomonari Kasai1, Yueguang Li4, Yuh Sugii1, Guoliang Jin1, Masashi Okada1, Arun Vaidyanath1, Akifumi Mizutani1, Ayano Satoh5, Takayuki Kudoh1, Mary J. C. Hendrix6, David S. Salomon7, Li Fu8*, Masaharu Seno1*
Cancer stem cells (CSCs) are capable of continuous proliferation and self-renewal and are proposed to play significant roles in oncogenesis, tumor growth, metastasis and cancer recurrence. CSCs are considered derived from normal stem cells affected by the tumor microenvironment although the mechanism of development is not clear yet. In 2007, Yamanaka's group succeeded in generating Nanog mouse induced pluripotent stem (miPS) cells, in which green fluorescent protein (GFP) has been inserted into the 5′-untranslated region of the Nanog gene. Usually, iPS cells, just like embryonic stem cells, are considered to be induced into progenitor cells, which differentiate into various normal phenotypes depending on the normal niche. We hypothesized that CSCs could be derived from Nanog miPS cells in the conditioned culture medium of cancer cell lines, which is a mimic of carcinoma microenvironment. As a result, the Nanog miPS cells treated with the conditioned medium of mouse Lewis lung carcinoma acquired characteristics of CSCs, in that they formed spheroids expressing GFP in suspension culture, and had a high tumorigenicity in Balb/c nude mice exhibiting angiogenesis in vivo. In addition, these iPS-derived CSCs had a capacity of self-renewal and expressed the marker genes, Nanog, Rex1, Eras, Esg1 and Cripto, associated with stem cell properties and an undifferentiated state. Thus we concluded that a model of CSCs was originally developed from miPS cells and proposed the conditioned culture medium of cancer cell lines might perform as niche for producing CSCs. The model of CSCs and the procedure of their establishment will help study the genetic alterations and the secreted factors in the tumor microenvironment which convert miPS cells to CSCs. Furthermore, the identification of potentially bona fide markers of CSCs, which will help the development of novel anti-cancer therapies, might be possible though the CSC model.
