生物谷報道：最近,，約翰.霍普金斯大學和米蘭大學的科學家有力的證實了他們能夠利用某種蛋白阻斷小鼠模型中致死性人腦癌的發(fā)生,。這種蛋白能夠選擇性誘導某些類似腫瘤干細胞的活性發(fā)生改變,。這篇文章發(fā)表在這個星期的Nature雜志上,。
最普遍的腦細胞癌成膠質細胞瘤的特征是腫瘤組織中母細胞樣腦細胞的存在,，代替了對損傷細胞的修復機制,。母細胞與機體中其他細胞不同,，在正確“信號”的刺激下,，它們能發(fā)育形成任何一種細胞。 研究者正在研究針對它們的治療試驗,，這類試驗依賴一類骨形態(tài)發(fā)生蛋白,，即成膠質細胞瘤用骨形態(tài)發(fā)生蛋白4（BMP4）。這種蛋白引起神經母細胞樣簇失去母細胞的特性,，從而終止了它們的分化能力,。
首先,，研究者對人成膠質細胞瘤用骨形態(tài)發(fā)生蛋白4（BMP4）預處理，,，然后將這些處理的細胞注射入鼠腦,。注射未預處理瘤細胞的小鼠發(fā)生了廣泛、侵襲性腫瘤,，而注射BMP4處理瘤細胞的小鼠沒有腫瘤的發(fā)生,。3、4個月過后,，感染未處理細胞的小鼠全部死亡,，而用BMP4處理細胞感染的小鼠幾乎全部存活了下來。其次,，給小鼠植入膠質瘤細胞后,，科學家再將一種可以緩慢釋放BMP4的珠狀物直接注入小鼠腦細胞中。被注入不含任何物質的珠狀物小鼠發(fā)生廣泛惡性腫瘤并死亡,，而含有BMP4珠狀物的小鼠生存時間長很多,，而且80%的小鼠在癌細胞注入后生存時間仍長達4個月。
“我們的想法是在病人手術后采用BMP4或者類似物質處理,，徹底去除成膠質細胞瘤從而防止復發(fā)以及延長生存時間,。”醫(yī)學博士 Alessandro Olivi說道,。Alessandro Olivi是霍普金斯神經外科腫瘤學部門主任,，同時也是這個項目的資助者。這個想法的依據(jù)就是BMPs 能夠通過減少母細胞樣群阻止成膠質細胞瘤,，這為以后處理和治療類似破壞性疾病開辟了一條令人興奮的途徑,。
FIGURE 1. Expression and activation of BMP receptors in human GBM cells.
a, Messenger RNA transcripts for BMP receptors and BMP4. Lane 1, negative control; lane 2, acutely dissociated GBM CD133+ cells; lane 3, briefly cultured CD133+ cells; lane 4, MCF7 cells (positive control). b–g, BMPR immunoreactivity in acutely isolated (b–d) or briefly cultured (e–g) CD133+ cells. h–j, Phosphorylation of Smad proteins (using anti-phospho(p)Smad1,5,8) after exposure of briefly cultured cells to BMP4 for 30 min (h), 60 min (i) or 90 min (j) (Supplementary Fig. 2b; Supplementary Table a). b–j, Scale bar, 15 m, as in j. k–p, Western blotting. k, BMP4 in acutely dissociated (left) or briefly cultured CD133+ cells (right). l, Unchanged Smad1 levels in BMP4-treated (right), briefly cultured cells (left, untreated control). m, n, Increased Smad1,5,8 phosphorylation by BMP4 (left, untreated control; right, BMP4-treated) in acutely dissociated (m) or briefly cultured (n) cells. o, p, Increased Smad4 expression in briefly cultured (o) or acutely dissociated (p) cells by BMP4 (untreated control, left; BMP4-treated, right).
原文出處：
Nature Volume 444 Number 7120 p761－765
Bone morphogenetic proteins inhibit the tumorigenic potential of human brain tumour-initiating cells p761
S. G. M. Piccirillo, B. A. Reynolds, N. Zanetti, G. Lamorte, E. Binda, G. Broggi, H. Brem, A. Olivi, F. Dimeco and A. L. Vescovi
doi:10.1038/nature05349
First paragraph | Full Text | PDF (1,243K) | Supplementary information
See also: News and Views by Dirks
相關基因 (Pubmed Gene)
BMP4
Official Symbol: BMP4 and Name: bone morphogenetic protein 4 [Homo sapiens]
Other Aliases: BMP2B, BMP2B1, ZYME
Other Designations: bone morphogenetic protein 2B
Chromosome: 14; Location: 14q22-q23
MIM: 112262
GeneID: 652
