麻省理工學(xué)院的Janet M. Tse等近日在《美國(guó)國(guó)家科學(xué)院院刊》（Proceedings of the National Academy of Sciences）發(fā)表論文稱(chēng),，機(jī)械擠壓作用或可促進(jìn)腫瘤細(xì)胞轉(zhuǎn)移,。
腫瘤細(xì)胞在體內(nèi)進(jìn)行不受機(jī)體控制的增殖分裂,，當(dāng)其分裂數(shù)量到達(dá)一定程度后,，腫瘤細(xì)胞便受到有限的空間帶來(lái)的擠壓。為了研究這種擠壓作用對(duì)腫瘤細(xì)胞的影響,，Janet Tse等將乳腺上皮細(xì)胞置于一層膜表面,，并使用活塞對(duì)其進(jìn)行擠壓。
研究者發(fā)現(xiàn),，擠壓作用可通過(guò)刺激細(xì)胞層邊緣中首先轉(zhuǎn)移的"領(lǐng)頭羊"細(xì)胞的形成,，從而促進(jìn)乳腺癌細(xì)胞的遷移。
"領(lǐng)頭羊"細(xì)胞可在轉(zhuǎn)移過(guò)程中在保持與拖尾細(xì)胞保持聯(lián)系的同時(shí),，擴(kuò)大向遷移方向的突出,。
此外,，擠壓作用可誘導(dǎo)腫瘤細(xì)胞分泌一種稱(chēng)為纖維連接蛋白的蛋白質(zhì)，該蛋白質(zhì)可通過(guò)增強(qiáng)細(xì)胞與細(xì)胞間和細(xì)胞與膜表面間的粘連,，從而促進(jìn)腫瘤細(xì)胞的遷移和"領(lǐng)頭羊"細(xì)胞的形成,。
研究者指出，高度侵襲性腫瘤細(xì)胞通常受到擠壓作用的影響,，這或許是由于這些細(xì)胞已經(jīng)隨時(shí)準(zhǔn)備好去改變這種受擠壓的環(huán)境了,。
作者稱(chēng)，腫瘤在生長(zhǎng)過(guò)程中受到的擠壓作用可通過(guò)刺激"領(lǐng)頭羊"細(xì)胞的形成而發(fā)生遷移,，造成腫瘤轉(zhuǎn)移,。機(jī)械擠壓作用機(jī)制為阻止腫瘤遷移和浸潤(rùn)提供了一個(gè)新的靶點(diǎn)。（生物谷bioon.com）
doi:10.1073/pnas.1118910109
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Mechanical compression drives cancer cells toward invasive phenotype
Janet M. Tse, Gang Cheng, James A. Tyrrell,Sarah A. Wilcox-Adelman, Yves Boucher, Rakesh K. Jain, and Lance L. Munn.
Uncontrolled growth in a confined space generates mechanical compressive stress within tumors, but little is known about how such stress affects tumor cell behavior. Here we show that compressive stress stimulates migration of mammary carcinoma cells. The enhanced migration is accomplished by a subset of "leader cells" that extend filopodia at the leading edge of the cell sheet. Formation of these leader cells is dependent on cell microorganization and is enhanced by compressive stress. Accompanied by fibronectin deposition and stronger cell-matrix adhesion, the transition to leader-cell phenotype results in stabilization of persistent actomyosin-independent cell extensions and coordinated migration. Our results suggest that compressive stress accumulated during tumor growth can enable coordinated migration of cancer cells by stimulating formation of leader cells and enhancing cell-substrate adhesion. This novel mechanism represents a potential target for the prevention of cancer cell migration and invasion.
