生物谷Bioon.net 訊 斯坦福大學(xué)醫(yī)學(xué)院的科學(xué)家獲得了一項有意義的發(fā)現(xiàn),，他們識別了人類黑素瘤的腫瘤起源細(xì)胞,。在這種具有攻擊性的皮膚癌中，腫瘤起源細(xì)胞的存在爭論已久,。這項發(fā)現(xiàn)同樣能夠解釋,，在預(yù)防人類疾病復(fù)發(fā)過程中，目前大部分免疫療法不成功的原因,。
"這些細(xì)胞缺乏常規(guī)黑素瘤細(xì)胞的表面標(biāo)記,，而這些標(biāo)記在治療過程中可以被靶向定位。不能消除癌癥根源細(xì)胞的療法將會是失敗的,。"這項研究負(fù)責(zé)人Alexander Boiko博士表示,。研究結(jié)果發(fā)布在7月1日的Nature雜志上。
腫瘤干細(xì)胞理論認(rèn)為,，腫瘤干細(xì)胞就像蜂巢中的蜂王,，且只有一小部分癌細(xì)胞位于腫瘤生長的"根部"。這些細(xì)胞都能自我更新并分化成其他類型的腫瘤細(xì)胞,。
任何不能消除根源細(xì)胞的癌癥療法都不能完全根治疾病,，即使殺滅了幾乎所有其他的細(xì)胞。這也就是減輕癌癥患者癥狀相對簡單,，而阻止數(shù)月或數(shù)年后癌癥干細(xì)胞再次發(fā)威非常困難的原因,。生物谷啟用新域名 www.bioon.net
盡管越來越多的證據(jù)支持癌癥干細(xì)胞假說，而黑素瘤任然是一個難題,。2008年密歇根大學(xué)的一項研究發(fā)現(xiàn)在免疫缺乏的老鼠中,，4個黑素瘤細(xì)胞中就有一個會導(dǎo)致癌癥發(fā)生，這表明或許在這種類型的腫瘤中并不存在癌癥干細(xì)胞這一特殊細(xì)胞群體,。Boiko則希望能夠揭開這個謎團(tuán),。
"我不知道黑素瘤是不是真的不存在腫瘤起源細(xì)胞，我完全不存在任何偏見，因此得到這樣一個清晰的答案我很驚喜,。它恰恰符合其他實體腫瘤的研究發(fā)現(xiàn),。"Boiko解釋說。
在這項研究中,，Boiko直接從患者身上獲取初始的黑素瘤樣本,，然后分析細(xì)胞表面標(biāo)記物。這種直接獲取腫瘤細(xì)胞的方法避免了實驗室中的細(xì)胞培養(yǎng),，而癌細(xì)胞的培養(yǎng)通常會使細(xì)胞有時間進(jìn)化使得研究人員不能精確識別細(xì)胞成分,。
最終,，Boiko發(fā)現(xiàn)了一種叫CD271的蛋白,，在檢測的人類黑素瘤樣本中，研究人員發(fā)現(xiàn)該蛋白總是在一小部分細(xì)胞中表達(dá),。樣本中細(xì)胞表達(dá)CD271的比例從2.5%到41%不等,，該標(biāo)記物出現(xiàn)在樣本細(xì)胞中的平均比率是16.7%。
接下來,，研究人員在實驗室中將這些從人類樣本中獲得的黑素瘤細(xì)胞移植到免疫力嚴(yán)重缺乏的老鼠身上,。相比于移植細(xì)胞后不表達(dá)CD271的老鼠,他們發(fā)現(xiàn)表達(dá)CD271的細(xì)胞更易導(dǎo)致癌癥發(fā)生，這個比率分別是70%和7%,。另外,，僅有一個新產(chǎn)生的腫瘤不是由于移植了CD271陽性細(xì)胞導(dǎo)致的，這表明含有這個標(biāo)記的細(xì)胞能夠自我更新并分化形成其他類型的腫瘤細(xì)胞,。
研究人員將正常人類皮膚移植到免疫系統(tǒng)受損的老鼠背部,，并在皮膚中注入黑素瘤細(xì)胞。結(jié)果發(fā)現(xiàn),，只有那些注入了能表達(dá)CD271的細(xì)胞的老鼠形成了腫瘤并出現(xiàn)肺轉(zhuǎn)移,。
對于是否腫瘤起源細(xì)胞也會表達(dá)常見細(xì)胞抗原，研究人員發(fā)現(xiàn)表達(dá)CD271的細(xì)胞或完全或部分缺失TYR, MART和MAGE這三種常見治療靶標(biāo)的表達(dá)能力,，在黑素瘤患者中的缺失比例分別是86%,，69%和68%。這大概也是黑素瘤患者經(jīng)常復(fù)發(fā)的原因,。
Boiko博士認(rèn)為,，利用這項研究結(jié)果有望開發(fā)療法，靶向定位表達(dá)CD271的細(xì)胞,。通過聯(lián)合療法或能有效殺死腫瘤中的兩種細(xì)胞以預(yù)防疾病的復(fù)發(fā),。（生物谷Bioon.net）
生物谷推薦原文出處：
Nature doi:10.1038/nature09161
Human melanoma-initiating cells express neural crest nerve growth factor receptor CD271
Alexander D. Boiko1, Olga V. Razorenova2, Matt van de Rijn3, Susan M. Swetter4,5, Denise L. Johnson6,9, Daphne P. Ly6,7, Paris D. Butler6,7, George P. Yang5,6,7, Benzion Joshua8, Michael J. Kaplan8, Michael T. Longaker1,6,7 & Irving L. Weissman1,3
The question of whether tumorigenic cancer stem cells exist in human melanomas has arisen in the last few years1. Here we show that in melanomas, tumour stem cells (MTSCs, for melanoma tumour stem cells) can be isolated prospectively as a highly enriched CD271+ MTSC population using a process that maximizes viable cell transplantation1, 2. The tumours sampled in this study were taken from a broad spectrum of sites and stages. High-viability cells isolated by fluorescence-activated cell sorting and re-suspended in a matrigel vehicle were implanted into T-, B- and natural-killer-deficient Rag2?/?γc?/? mice. The CD271+ subset of cells was the tumour-initiating population in 90% (nine out of ten) of melanomas tested. Transplantation of isolated CD271+ melanoma cells into engrafted human skin or bone in Rag2?/?γc?/? mice resulted in melanoma; however, melanoma did not develop after transplantation of isolated CD271? cells. We also show that in mice, tumours derived from transplanted human CD271+ melanoma cells were capable of metastatsis in vivo. CD271+ melanoma cells lacked expression of TYR, MART1 and MAGE in 86%, 69% and 68% of melanoma patients, respectively, which helps to explain why T-cell therapies directed at these antigens usually result in only temporary tumour shrinkage.
1Institute for Stem Cell Biology and Regenerative Medicine, Stanford Cancer Center, Stanford University School of Medicine, Stanford, California 94304-5542, USA
2Department of Radiation Oncology, Stanford University Medical Center, Stanford Cancer Center, Stanford, California 94305-5118, USA
3Department of Pathology, Stanford University Medical Center, Stanford Cancer Center, Stanford, California 94305-5118, USA
4Department of Dermatology, Pigmented Lesion and Melanoma Program, Stanford University Medical Center, Stanford Cancer Center, Stanford, California 94305-5118, USA
5Veterans Affairs Palo Alto Health Care System, Palo Alto, California 94304, USA
6Department of Surgery, Stanford University Medical Center, Stanford Cancer Center, Stanford, California 94305-5118, USA
7Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, California 94305-5118, USA
8Department of Otolaryngology-Head and Neck Surgery, Stanford University Medical Center, Stanford Cancer Center, Stanford, California 94305-5118, USA
