研究人員發(fā)現(xiàn),，原始膀胱癌細(xì)胞會(huì)用“不要吃掉我”的信號(hào)做掩飾，把免疫細(xì)胞嚇跑,，以便它們能在稍后發(fā)育成熟,，形成腫瘤。
不過(guò)研究人員已經(jīng)發(fā)現(xiàn)一種撕下膀胱癌細(xì)胞這種偽裝術(shù)的方法,，他們表示,，這項(xiàng)發(fā)現(xiàn)或許有助于形成能治療幾種不同癌腫的新方法。現(xiàn)在最要緊的是要找到一種方法,，把那些患有非常危險(xiǎn)的膀胱癌的患者,，跟那些患有良性腫瘤的人分開(kāi)。大部分膀胱癌生長(zhǎng)緩慢,，易于治療,，但是有15%容易擴(kuò)散，具有很大的致命性,。
加利福尼亞州斯坦福大學(xué)的歐文·維斯曼(Irving Weissman)博士和同事們發(fā)現(xiàn),，所謂的腫瘤干細(xì)胞(cancer stem cells)竟用CD-47蛋白質(zhì)偽裝自己。被稱(chēng)作巨噬細(xì)胞的免疫細(xì)胞通常會(huì)吃掉癌細(xì)胞,，但是CD-47是避開(kāi)它們的信號(hào),。維斯曼在一份聲明中說(shuō)：“這是我們第一次在腫瘤干細(xì)胞里發(fā)現(xiàn)‘不要吃掉我’的信號(hào)。我們正在加緊查看其他腫瘤細(xì)胞的步伐,，看一看這是不是所有或者大部分腫瘤干細(xì)胞慣用的策略,。”
該科研組早些時(shí)候發(fā)現(xiàn)，相同類(lèi)型的白血病細(xì)胞也用CD-47偽裝自己,。膀胱腫瘤樣本顯示,，大部分腫瘤細(xì)胞都含有豐富的CD-47蛋白。維斯曼的科研組發(fā)現(xiàn),，繼續(xù)惡化,，形成非常危險(xiǎn)的膀胱腫瘤的患者的癌細(xì)胞里的CD-47的傳遞速度更快，這意味著該蛋白更加活躍,。他們認(rèn)為,，他們可以利用這種罕見(jiàn)模式更好地幫助患者進(jìn)行診斷，讓那些擁有擴(kuò)散性更強(qiáng)的癌細(xì)胞的患者能更及時(shí)的得到治療,。
維斯曼的科研組在美國(guó)《國(guó)家科學(xué)院院刊》（PNAS）上的報(bào)告里寫(xiě)道,，他們還利用一種單克隆抗體(可以識(shí)別單一蛋白的一種免疫系統(tǒng)粒子)來(lái)防止CD-47偽裝,。有抗體的實(shí)驗(yàn)室器皿里的腫瘤細(xì)胞，不久后就被巨噬細(xì)胞消滅了,。包括MabThera,、赫賽汀(Herceptin)和阿瓦斯汀(Avastin)在內(nèi)的幾種抗癌藥物都包含單克隆抗體。（生物谷Bioon.com）
生物谷推薦原始出處：
PNAS August 4, 2009, doi: 10.1073/pnas.0906549106
Identification, molecular characterization, clinical prognosis, and therapeutic targeting of human bladder tumor-initiating cells
Keith Syson Chana,b,1, Inigo Espinosac, Mark Chaoa, David Wongd, Laurie Aillesa, Max Diehna, Harcharan Gillb, Joseph Presti, Jr.b, Howard Y. Changd, Matt van de Rijnc, Linda Shortliffeb and Irving L. Weissmana,1
aInstitute for Stem Cell Biology and Regenerative Medicine, Stanford Cancer Center, Stanford University School of Medicine, Stanford, CA 94304-5542;
Departments of bUrology and
cPathology, Stanford University Medical Center, Stanford, CA 94305-5118; and
dProgram in Epithelial Biology, Stanford University, Stanford, CA 94305
Major clinical issues in bladder cancer include the identification of prediction markers and novel therapeutic targets for invasive bladder cancer. In the current study, we describe the isolation and characterization of a tumor-initiating cell (T-IC) subpopulation in primary human bladder cancer, based on the expression of markers similar to that of normal bladder basal cells (Lineage-CD44+CK5+CK20?). The bladder T-IC subpopulation was defined functionally by its enriched ability to induce xenograft tumors in vivo that recapitulated the heterogeneity of the original tumor. Further, molecular analysis of more than 300 bladder cancer specimens revealed heterogeneity among activated oncogenic pathways in T-IC (e.g., 80% Gli1, 45% Stat3, 10% Bmi-1, and 5% β-catenin). Despite this molecular heterogeneity, we identified a unique bladder T-IC gene signature by gene chip analysis. This T-IC gene signature, which effectively distinguishes muscle-invasive bladder cancer with worse clinical prognosis from non-muscle-invasive (superficial) cancer, has significant clinical value. It also can predict the progression of a subset of recurring non-muscle-invasive cancers. Finally, we found that CD47, a protein that provides an inhibitory signal for macrophage phagocytosis, is highly expressed in bladder T-ICs compared with the rest of the tumor. Blockade of CD47 by a mAb resulted in macrophage engulfment of bladder cancer cells in vitro. In summary, we have identified a T-IC subpopulation with potential prognostic and therapeutic value for invasive bladder cancer.
