如果一個(gè)上皮細(xì)胞層要保持其結(jié)構(gòu),，并且為機(jī)體提供一個(gè)保護(hù)壁壘,，它就需要在正在分裂的細(xì)胞數(shù)量與正在死亡的細(xì)胞數(shù)量之間維持平衡。雖然補(bǔ)償細(xì)胞的分裂可能被死亡細(xì)胞所觸發(fā),，但是,，細(xì)胞死亡如何減輕細(xì)胞增殖所帶來(lái)的“擁擠”，目前尚不明了,。
4月26日出版的《自然》雜志同時(shí)發(fā)表了兩篇有關(guān)上皮組織細(xì)胞數(shù)量控制的文章,，指出維持上皮組織細(xì)胞平衡的機(jī)理可能與癌癥有關(guān)。
英國(guó)倫敦大學(xué)學(xué)院分子細(xì)胞學(xué)實(shí)驗(yàn)室的Buzz Baum及其同事研究了果蠅組織中的這一過(guò)程,，并在一個(gè)組織中的物理力與細(xì)胞損失的速度之間發(fā)現(xiàn)了一個(gè)直接聯(lián)系,。Baum研究小組的實(shí)驗(yàn)報(bào)告顯示，在過(guò)分“擁擠”的組織區(qū)域里,，一些細(xì)胞的“細(xì)胞粘性連接點(diǎn)”就會(huì)損失,，并被相鄰細(xì)胞擠出去。
活細(xì)胞分層的這一過(guò)程使上皮細(xì)胞能夠緩沖生長(zhǎng)中所發(fā)生的變化,，并幫助實(shí)現(xiàn)正常的組織平衡,。作為上皮增生與細(xì)胞分裂之間的一個(gè)聯(lián)系，它可能與癌癥發(fā)育的早期階段有關(guān),。
另一方面,，刊登在同期《自然》雜志上的第二篇論文指出,，美國(guó)猶他州大學(xué)癌癥研究所腫瘤學(xué)系的Jody Rosenblatt及其同事研究了上皮細(xì)胞單層，發(fā)現(xiàn)上皮在高度緊張的地方會(huì)將活細(xì)胞而不是正在死亡的細(xì)胞擠出去,。而被擠出去的細(xì)胞會(huì)因?yàn)榇婊钜蜃拥氖ザ劳觥?/p>
因此,，“擠出”可能提供一個(gè)腫瘤抑制機(jī)制，該機(jī)制可能被用來(lái)消除過(guò)剩的細(xì)胞,。然而在具有高水平的存活信號(hào)通道的癌癥中,，“擠出”可能會(huì)促進(jìn)腫瘤細(xì)胞入侵。（生物谷 bioon.com）
doi:10.1038/nature10984
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Live-cell delamination counterbalances epithelial growth to limit tissue overcrowding
Eliana Marinari,Aida Mehonic,Scott Curran,Jonathan Gale,Thomas Duke& Buzz Baum
The development and maintenance of an epithelium requires finely balanced rates of growth and cell death. However, the mechanical and biochemical mechanisms that ensure proper feedback control of tissue growth1, 2, 3, 4, which when deregulated contribute to tumorigenesis, are poorly understood. Here we use the fly notum as a model system5 to identify a novel process of crowding-induced cell delamination that balances growth to ensure the development of well-ordered cell packing. In crowded regions of the tissue, a proportion of cells undergo a serial loss of cell–cell junctions and a progressive loss of apical area, before being squeezed out by their neighbours. This path of delamination is recapitulated by a simple computational model of epithelial mechanics, in which stochastic cell loss relieves overcrowding as the system tends towards equilibrium. We show that this process of delamination is mechanistically distinct from apoptosis-mediated cell extrusion6, 7, 8 and precedes the first signs of cell death. Overall, this analysis reveals a simple mechanism that buffers epithelia against variations in growth. Because live-cell delamination constitutes a mechanistic link between epithelial hyperplasia and cell invasion, this is likely to have important implications for our understanding of the early stages of cancer development.
doi:10.1038/nature10999
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Crowding induces live cell extrusion to maintain homeostatic cell numbers in epithelia
George T. Eisenhoffer,Patrick D. Loftus,Masaaki Yoshigi,Hideo Otsuna,Chi-Bin Chien,Paul A. Morcos& Jody Rosenblatt
For an epithelium to provide a protective barrier, it must maintain homeostatic cell numbers by matching the number of dividing cells with the number of dying cells. Although compensatory cell division can be triggered by dying cells1, 2, 3, it is unknown how cell death might relieve overcrowding due to proliferation. When we trigger apoptosis in epithelia, dying cells are extruded to preserve a functional barrier4. Extrusion occurs by cells destined to die signalling to surrounding epithelial cells to contract an actomyosin ring that squeezes the dying cell out4, 5, 6. However, it is not clear what drives cell death during normal homeostasis. Here we show in human, canine and zebrafish cells that overcrowding due to proliferation and migration induces extrusion of live cells to control epithelial cell numbers. Extrusion of live cells occurs at sites where the highest crowding occurs in vivo and can be induced by experimentally overcrowding monolayers in vitro. Like apoptotic cell extrusion, live cell extrusion resulting from overcrowding also requires sphingosine 1-phosphate signalling and Rho-kinase-dependent myosin contraction, but is distinguished by signalling through stretch-activated channels. Moreover, disruption of a stretch-activated channel, Piezo1, in zebrafish prevents extrusion and leads to the formation of epithelial cell masses. Our findings reveal that during homeostatic turnover, growth and division of epithelial cells on a confined substratum cause overcrowding that leads to their extrusion and consequent death owing to the loss of survival factors. These results suggest that live cell extrusion could be a tumour-suppressive mechanism that prevents the accumulation of excess epithelial cells.
