2012年9月6日 訊 /生物谷BIOON/ --莫菲特癌癥中心以及南佛羅里達(dá)大學(xué)和韋恩州立大學(xué)（Wayne State University）的研究人員已經(jīng)發(fā)現(xiàn)，腫瘤細(xì)胞的生存依賴于腫瘤酸性微環(huán)境。他們研究發(fā)現(xiàn)酸度對(duì)乳腺癌和胰腺癌細(xì)胞株的影響自噬在酸性的微環(huán)境的重要性,。
這項(xiàng)研究發(fā)表在8月15日的美國(guó)癌癥研究協(xié)會(huì)Cancer Research雜志上。Robert J. Gillies博士說(shuō)：癌癥的發(fā)展是一個(gè)多步驟過(guò)程,，其發(fā)生發(fā)展過(guò)程受到某些物理性質(zhì)如腫瘤微環(huán)境的影響。
低氧和高酸度對(duì)細(xì)胞是有毒性的,。而這項(xiàng)研究表明,，在這些壓力條件下，腫瘤細(xì)胞通過(guò)自噬適應(yīng)這些微環(huán)境存活,、增殖,，并最終發(fā)生轉(zhuǎn)移。據(jù)作者的觀點(diǎn),，到目前為止沒有多少人了解細(xì)胞在酸性條件下的生存機(jī)制,，但它已經(jīng)有研究證實(shí)酸中毒可改變基因的表達(dá)導(dǎo)致細(xì)胞向適合在低pH值條件下生長(zhǎng)和存活的表型轉(zhuǎn)變。
研究人員說(shuō)明確低pH條件下腫瘤的生存機(jī)制后方便我們進(jìn)一步了解腫瘤的發(fā)展以及開發(fā)出新的治療策略,。在這項(xiàng)研究中,，研究人員檢測(cè)發(fā)現(xiàn)腫瘤細(xì)胞株在酸性條件下更會(huì)學(xué)習(xí)如何通過(guò)細(xì)胞自噬和適應(yīng)。他們指出,，在酸性環(huán)境中,，正常細(xì)胞可以通過(guò)增加細(xì)胞死亡信號(hào)途徑適應(yīng)酸性應(yīng)力，而這同樣是癌癥細(xì)胞生存和自適應(yīng)所需要的機(jī)制,。
癌癥的一個(gè)標(biāo)志是癌細(xì)胞逃避細(xì)胞凋亡的能力,。在腫瘤發(fā)生的不同階段，自噬在某些特定情況下會(huì)促進(jìn)腫瘤的生存,。他們的研究表明,，自噬對(duì)乳腺癌和胰腺癌細(xì)胞株適應(yīng)低pH值環(huán)境非常重要。據(jù)研究人員介紹,，他們發(fā)現(xiàn)了一個(gè)潛在的自噬抑制劑來(lái)治療腫瘤,，該抑制劑不影響在中性PH環(huán)境下的細(xì)胞,。（生物谷：Bioon.com）
doi:10.1158/0008-5472.CAN-11-3881
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Chronic Autophagy Is a Cellular Adaptation to Tumor Acidic pH Microenvironments.
J. W. Wojtkowiak, J. M. Rothberg, V. Kumar, K. J. Schramm, E. Haller, J. B. Proemsey, M. C. Lloyd, B. F. Sloane, R. J. Gillies.
Researchers at Moffitt Cancer Center and colleagues at the University of South Florida and Wayne State University have discovered that tumor cell survival relies on adaptation to acidic conditions in the tumor microenvironment. Their research investigating the effects of acidity on breast and pancreatic cancer cell lines revealed the importance of autophagy in acidic microenvironments and suggests that a successful treatment strategy might be based on this autophagic dependence.The study appears as the cover story for the Aug. 15 issue of Cancer Research, a publication of the American Association for Cancer Research.Cancer progression is a multistep process strongly influenced by the physical properties of the tumor microenvironment," said Robert J. Gillies, Ph.D., corresponding author of the study and chair of Moffitt's Department of Cancer Imaging and Metabolism. "Both low oxygen and high acidity can be cytotoxic. Our research suggests that adaptation to these stressful conditions involves autophagy allowing cancer cells to survive, proliferate and eventually metastasize to secondary sites.
