由于癌細(xì)胞的無限生長,普遍觀點(diǎn)認(rèn)為衰老可能能夠阻止腫瘤生長,并可能作為一種方法用于治療癌癥.意大利米蘭大學(xué)的一位癌癥生物學(xué)家與另兩位分別來自意大利國家研究理事會(huì)和康奈爾大學(xué)的物理學(xué)家之間展開了合作,研究表明,細(xì)胞衰老自發(fā)性地出現(xiàn)于黑色素瘤細(xì)胞中,但不會(huì)停止它們的生長,這是由一小部分的癌癥干細(xì)胞維持著.研究結(jié)果發(fā)表于1月19日的PLoS Computational Biology期刊上,研究解釋了為什么單靠誘導(dǎo)癌細(xì)胞衰老很難治療癌癥.
這項(xiàng)工作探討了黑色素瘤和衰老之間的關(guān)系.在正常過程中,在達(dá)到成熟后細(xì)胞開始衰老并最終停止復(fù)制.研究人員對(duì)黑色素瘤細(xì)胞群的長期進(jìn)化進(jìn)行了追蹤,檢測(cè)衰老細(xì)胞的數(shù)量.三個(gè)月后,癌細(xì)胞生長減慢并且大部分的細(xì)胞變得衰老,然而生長并沒有停止,并最終恢復(fù)了起始生長速度直到衰老的細(xì)胞幾乎消失.
作者用癌癥干細(xì)胞假想對(duì)實(shí)驗(yàn)數(shù)據(jù)進(jìn)行了數(shù)學(xué)建模,在這個(gè)假想中,其中一小組癌細(xì)胞無限期地進(jìn)行復(fù)制,因而不受衰老的影響.這些癌癥干細(xì)胞產(chǎn)生了一個(gè)較大癌細(xì)胞群體,而這些癌細(xì)胞只能進(jìn)行有限次數(shù)的復(fù)制.這個(gè)模型間接的確認(rèn)了黑色素瘤中癌癥干細(xì)胞的存在,這是一個(gè)在癌癥研究界一直爭(zhēng)論著的問題.
盡管很大一部分癌細(xì)胞易于衰老,研究人員得出結(jié)論,誘導(dǎo)衰老不可能提供一個(gè)成功的治療策略,因?yàn)檫@些細(xì)胞與腫瘤的生長無關(guān).然而,在黑色素瘤中腫瘤干細(xì)胞存在的間接證據(jù)可能引發(fā)新療法的開發(fā)來治療特定類型的癌癥.挑戰(zhàn)將會(huì)是癌癥干細(xì)胞對(duì)藥物誘導(dǎo)衰老的強(qiáng)烈抵抗.沿著這條線的研究,腫瘤治療將側(cè)重于針對(duì)這些癌癥干細(xì)胞而非每一個(gè)癌細(xì)胞.(生物谷bioon.com)
doi:10.1371/journal.pcbi.1002316
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Senescent Cells in Growing Tumors: Population Dynamics and Cancer Stem Cells
La Porta CAM, Zapperi S, Sethna JP
Abstract: Tumors are defined by their intense proliferation, but sometimes cancer cells turn senescent and stop replicating. In the stochastic cancer model in which all cells are tumorigenic, senescence is seen as the result of random mutations, suggesting that it could represent a barrier to tumor growth. In the hierarchical cancer model a subset of the cells, the cancer stem cells, divide indefinitely while other cells eventually turn senescent. Here we formulate cancer growth in mathematical terms and obtain predictions for the evolution of senescence. We perform experiments in human melanoma cells which are compatible with the hierarchical model and show that senescence is a reversible process controlled by survivin. We conclude that enhancing senescence is unlikely to provide a useful therapeutic strategy to fight cancer, unless the cancer stem cells are specifically targeted.
