近來研究表明,，骨髓樣細(xì)胞可使遠(yuǎn)處器官易于接受擴(kuò)散腫瘤細(xì)胞的集落形成,。然而，其具體機(jī)制一直不明,。5月14日Cancer Cell報(bào)道了Hua Yu研究組的論文"S1PR1-STAT3 Signaling Is Crucial for Myeloid Cell Colonization at Future Metastatic Sites"揭示了其分子機(jī)制,。
研究者發(fā)現(xiàn),，在腫瘤細(xì)胞中神經(jīng)鞘氨醇-1-磷酸化受體-1（S1PR1）-STAT3信號通路上調(diào)可激活腫瘤轉(zhuǎn)移靶部位細(xì)胞的S1PR1-STAT3水平，在機(jī)體遠(yuǎn)處組織造成易于接受轉(zhuǎn)移腫瘤的微環(huán)境,。抑制S1PR1或者STAT3在骨髓樣細(xì)胞中的功能可破壞已存在的易轉(zhuǎn)移微環(huán)境,。
S1PR1-STAT3信號通路的激活使骨髓樣細(xì)胞能穿過血管，在遠(yuǎn)處器官形成利于腫瘤轉(zhuǎn)移的微環(huán)境并且介導(dǎo)其自身及其他基質(zhì)細(xì)胞持續(xù)的存活和增殖,。對腫瘤患者不含腫瘤細(xì)胞的淋巴結(jié)的分析發(fā)現(xiàn),，與正常人的淋巴結(jié)細(xì)胞相比，腫瘤患者的標(biāo)本呈現(xiàn)更高的骨髓樣細(xì)胞浸潤,，STAT3的高水平活化以及細(xì)胞存活信號的增強(qiáng),。（生物谷Bioon.com)
doi: 10.1016/j.ccr.2012.03.039
PMC:
PMID:
S1PR1-STAT3 Signaling Is Crucial for Myeloid Cell Colonization at Future Metastatic Sites
Jiehui Deng, Yong Liu, Heehyoung Lee, Andreas Herrmann, Wang Zhang, Chunyan Zhang, Shudan Shen, Saul J. Priceman, Maciej Kujawski, Sumanta K. Pal, Andrew Raubitschek, Dave S.B. Hoon, Stephen Forman, Robert A. Figlin, Jie Liu, Richard Jove, Hua Yu
Recent studies underscore the importance of myeloid cells in rendering distant organs hospitable for disseminating tumor cells to colonize. However, what enables myeloid cells to have an apparently superior capacity to colonize distant organs is unclear. Here, we show that S1PR1-STAT3 upregulation in tumor cells induces factors that activate S1PR1-STAT3 in various cells in premetastatic sites, leading to premetastatic niche formation. Targeting either S1PR1 or STAT3 in myeloid cells disrupts existing premetastatic niches. S1PR1-STAT3 pathway enables myeloid cells to intravasate, prime the distant organ microenvironment and mediate sustained proliferation and survival of their own and other stromal cells at future metastatic sites. Analyzing tumor-free lymph nodes from cancer patients shows elevated myeloid infiltrates, STAT3 activity, and increased survival signal.
