小細(xì)胞肺癌的顯微鏡圖片,，圖片來(lái)自維基共享資源,。
RNA像DNA一樣是遺傳密碼的一部分，能夠指導(dǎo)細(xì)胞和最終指導(dǎo)身體如何形成,。來(lái)自英國(guó)倫敦大學(xué)圣喬治醫(yī)學(xué)院的研究人員證實(shí)癌細(xì)胞在全身發(fā)送的對(duì)癌癥生長(zhǎng)至關(guān)重要的溝通信號(hào)可能含有RNA片段,。他們還發(fā)現(xiàn)在早期這些遺傳指令能夠被化療截取和修飾從而有助于阻止癌細(xì)胞生長(zhǎng)。
鑒于當(dāng)前大多數(shù)抗癌治療方法直接攻擊癌細(xì)胞,，研究人員認(rèn)為這些發(fā)現(xiàn)給研究一種促進(jìn)機(jī)體免疫系統(tǒng)對(duì)抗疾病的新抗癌方法提供大量證據(jù),。然而，研究人員也強(qiáng)調(diào)這只是一項(xiàng)早期研究,，在最終讓病人受益之前還需開(kāi)展更多的研究,。這些研究發(fā)現(xiàn)發(fā)表在British Journal of Cancer期刊上。
人們認(rèn)為當(dāng)腫瘤細(xì)胞發(fā)展時(shí),，它們能夠產(chǎn)生在全身流通的化學(xué)分子以便指導(dǎo)機(jī)體產(chǎn)生適合腫瘤滋長(zhǎng)的理想環(huán)境,。這種環(huán)境的一個(gè)因素就是產(chǎn)生新血管，從而像它們對(duì)健康細(xì)胞那樣給腫瘤細(xì)胞提供營(yíng)養(yǎng),。
人們以前認(rèn)為這種血管形成(angiogenesis)過(guò)程是由稱(chēng)作細(xì)胞因子的化學(xué)信使觸發(fā)的,。但是基于在體外對(duì)人肺癌細(xì)胞開(kāi)展的實(shí)驗(yàn)研究，圣喬治醫(yī)學(xué)院研究人員發(fā)現(xiàn)腫瘤可能也發(fā)送RNA片段,，而且這些RNA片段像細(xì)胞因子那樣指導(dǎo)血管形成從而給腫瘤提供營(yíng)養(yǎng),。
研究人員繼續(xù)研究?jī)煞N經(jīng)常使用的處方抗癌藥---環(huán)磷酰胺(cyclophosphamide)和奧沙利鉑(oxaliplatin)---對(duì)血管形成的影響。他們收集未接受抗癌藥處理的癌細(xì)胞發(fā)送的RNA信息,，同時(shí)也收集已接受抗癌藥處理的癌細(xì)胞發(fā)送的這些信息,。
他們發(fā)現(xiàn)當(dāng)肺癌細(xì)胞接受奧沙利鉑處理時(shí)，腫瘤細(xì)胞產(chǎn)生的RNA和細(xì)胞因子信息不再能夠影響血管生長(zhǎng),。然而,，接受環(huán)磷酰胺處理的肺癌細(xì)胞仍然能夠通過(guò)這些化學(xué)信使指導(dǎo)血管給腫瘤輸送營(yíng)養(yǎng)。
該研究第一作者Wai Liu博士說(shuō),，“當(dāng)前,，藥物通過(guò)攻擊腫瘤細(xì)胞本身或者通過(guò)破壞腫瘤與身體之間的物理相互作用來(lái)對(duì)抗癌癥。然而只有極少數(shù)藥物靶向來(lái)自中腫瘤細(xì)胞和構(gòu)成腫瘤微環(huán)境的那些細(xì)胞之間發(fā)送的信號(hào),。部分上,，這是因?yàn)槿藗儗?duì)這些信號(hào)知之甚少,。這項(xiàng)研究告訴我們一些關(guān)于癌癥如何形成的信息并提供一種進(jìn)一步探索的途徑。它還提示著現(xiàn)存的藥物可能能夠以不同的方式對(duì)抗癌癥,。盡管這些只是初步的研究發(fā)現(xiàn),，而且確實(shí)還需要開(kāi)展更多研究，但是它們促進(jìn)人們?cè)阱憻捝眢w自己的免疫系統(tǒng)對(duì)抗癌癥方面越來(lái)越感興趣,，而且有望為未來(lái)利用這種方法開(kāi)出抗癌藥物提供基礎(chǔ),。” (生物谷：towersimper編譯)
doi:10.1038/bjc.2012.13
PMC:
PMID:
Supernatants derived from chemotherapy-treated cancer cell lines can modify angiogenesis
W M Liu, J L Dennis, A M Gravett, C Chanthirakumar, E Kaminska, G Coulton, D W Fowler, M Bodman-Smith and A G Dalgleish
background: There is evidence that tumours produce substances such as cytokines and microvesicular bodies bearing bioactive molecules, which support the carcinogenic process. Furthermore, chemotherapy has also been shown to modify these exudates and in doing so, neutralise their tumourigenic influence.
methods: In the current study, we have investigated the effect of chemotherapy agents on modifying the cytokine profile and microvesicular cargo of supernatants derived from cancer cell lines. In addition, we have explored the effect of these tumour-derived supernatants on angiogenesis, and how chemotherapy can alter the supernatants rendering them less pro-angiogenic.
results: Herein, we show that supernatants contain a rich cocktail of cytokines, a number of which are potent modulators of angiogenesis. They also contain microvesicular bodies containing RNA transcripts that code for proteins involved in transcription, immune modulation and angiogenesis. These supernatants altered intracellular signalling molecules in endothelial cells and significantly enhanced their tubulogenic character; however, this was severely compromised when supernatants from tumours treated with chemotherapy was used instead.
conclusion: This study suggests tumour exudates and bioactive material from tumours can influence cellular functions, and that treatment with some chemotherapy can serve to negate these pro-tumourigenic processes.
