轉(zhuǎn)移瘤的來源細(xì)胞依賴于適合于腫瘤轉(zhuǎn)移細(xì)胞克隆性繁殖的基質(zhì)微環(huán)境,，圖片來源和版權(quán)為瑞士洛桑理工大學(xué)瑞士實驗癌癥研究中心。
轉(zhuǎn)移瘤(即原發(fā)性腫瘤細(xì)胞轉(zhuǎn)移到新位點上形成的腫瘤)的增殖經(jīng)常是腫瘤導(dǎo)致的并發(fā)癥和死亡的主要原因,。來自瑞士洛桑理工大學(xué)瑞士實驗癌癥研究中心的研究小組第一次非常密切地研究這些轉(zhuǎn)移瘤本身的發(fā)展,，而不是集中注意在它們起源的原發(fā)性腫瘤(primary cancer),，分離出一種在轉(zhuǎn)移瘤發(fā)展中發(fā)揮關(guān)鍵中心的蛋白,，并且證實阻斷這種蛋白能夠阻止繼發(fā)性腫瘤(secondary cancer)的形成。2011年12月7日,，他們的研究成果提前在線發(fā)表在《自然》期刊上，為治療晚期階段癌癥打開新的治療方案之門,。
對轉(zhuǎn)移瘤細(xì)胞非常關(guān)鍵的一種蛋白
研究人員已經(jīng)知道一旦惡性腫瘤，腫瘤細(xì)胞在全身廣泛地擴(kuò)散,。然而,，這些細(xì)胞并不總是導(dǎo)致繼發(fā)性腫瘤的形成,。人們發(fā)現(xiàn)所有的癌細(xì)胞并不是同等構(gòu)建的：只有它們中一些稱作腫瘤干細(xì)胞(cancer stem cells)的細(xì)胞能夠啟動腫瘤轉(zhuǎn)移,。為此，它們必須在一個有利于它們發(fā)展的地方(即微環(huán)境)安營扎寨,。
研究環(huán)境能夠顯示幾個條件對于腫瘤擴(kuò)增是必不可少的。瑞士洛桑理工大學(xué)Debiopharm集團(tuán)腫瘤發(fā)生信號轉(zhuǎn)導(dǎo)主任Joerg Huelsken解釋道,，“特別是,，我們能夠在轉(zhuǎn)移瘤發(fā)展的微環(huán)境中分離出一種蛋白periostin,。沒有這種蛋白，腫瘤干細(xì)胞不能啟動腫瘤轉(zhuǎn)移，相反地,，它消失掉或保持休眠,。”
小鼠實驗中副作用最小化
蛋白periostin自然條件下作為胞外基質(zhì)的一部分而存在,，且在胎兒發(fā)育中發(fā)揮著作用。在成人中,，它只在特定器官---乳腺、骨,、皮膚和腸---中是有活性的。這項研究似乎證實它在腫瘤干細(xì)胞需要啟動腫瘤轉(zhuǎn)移的環(huán)境中發(fā)揮著一種關(guān)鍵性的作用,。培育出的缺乏這種蛋白的小鼠能夠抵抗腫瘤轉(zhuǎn)移形成。Huelsken說,，“我們已開發(fā)出一種附著到這種蛋白上的抗體,，使得這種蛋白不能發(fā)揮作用。我們希望這種方法能夠阻斷腫瘤轉(zhuǎn)移形成,。”
阻斷蛋白periostin的這些實驗在小鼠中很少產(chǎn)生副作用,。研究人員忠告道，“這并不一定意味著同樣的情形也將在人身上發(fā)生,。我們甚至不確定我們是否能夠找到在人身上發(fā)揮作用的同樣抗體。”
無論如何,，這一發(fā)現(xiàn)是非常鼓舞人心的,，特別是因為我們現(xiàn)在知道惡性腫瘤往往要比人們之前所想的要快很多,。因而阻斷腫瘤轉(zhuǎn)移發(fā)生似乎是能夠限制腫瘤有害影響的一個重要的治療方案,。(生物谷Bioon.com：towersimper編譯)
doi:10.1038/nature10694
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Interactions between cancer stem cells and their niche govern metastatic colonization
Ilaria Malanchi, Albert Santamaria-Martínez, Evelyn Susanto, Hong Peng, Hans-Anton Lehr, Jean-Francois Delaloye & Joerg Huelsken
Metastatic growth in distant organs is the major cause of cancer mortality. The development of metastasis is a multistage process with several rate-limiting steps. Although dissemination of tumour cells seems to be an early and frequent event, the successful initiation of metastatic growth, a process termed ‘metastatic colonization’, is inefficient for many cancer types and is accomplished only by a minority of cancer cells that reach distant sites. Prevalent target sites are characteristic of many tumour entities, suggesting that inadequate support by distant tissues contributes to the inefficiency of the metastatic process. Here we show that a small population of cancer stem cells is critical for metastatic colonization, that is, the initial expansion of cancer cells at the secondary site, and that stromal niche signals are crucial to this expansion process. We find that periostin (POSTN), a component of the extracellular matrix, is expressed by fibroblasts in the normal tissue and in the stroma of the primary tumour. Infiltrating tumour cells need to induce stromal POSTN expression in the secondary target organ (in this case lung) to initiate colonization. POSTN is required to allow cancer stem cell maintenance, and blocking its function prevents metastasis. POSTN recruits Wnt ligands and thereby increases Wnt signalling in cancer stem cells. We suggest that the education of stromal cells by infiltrating tumour cells is an important step in metastatic colonization and that preventing de novo niche formation may be a novel strategy for the treatment of metastatic disease.
