研究人員在日前在線出版的《自然—細(xì)胞生物學(xué)》期刊上報(bào)告說(shuō),，腫瘤轉(zhuǎn)移細(xì)胞利用一種機(jī)制侵入肺部，并在那里建立起次生腫瘤,。新研究鑒別出一種有潛力的藥物靶標(biāo),，可以預(yù)防癌癥的擴(kuò)散。
趨化因子是一種化學(xué)因子,，其功能是在感染發(fā)生時(shí)征集免疫細(xì)胞,。科學(xué)家們發(fā)現(xiàn),，原發(fā)腫瘤通過(guò)引入趨化因子為入侵肺部作準(zhǔn)備，這時(shí)趨化因子的作用是指引腫瘤細(xì)胞進(jìn)入“第二戰(zhàn)場(chǎng)”,。Hiratsuka和同事指出,，與此同時(shí)，原發(fā)腫瘤也誘導(dǎo)肺細(xì)胞產(chǎn)生一種名為血清淀粉樣蛋白A3(SAA3)附加因子,。通過(guò)啟動(dòng)與炎癥有關(guān)的一種基因,，SAA3加速了原發(fā)腫瘤細(xì)胞的征集,，促進(jìn)了趨化因子的產(chǎn)出,。重要的是，Hiratsuka研究小組發(fā)現(xiàn),，阻斷SAA3或其受體能降低小鼠肺部腫瘤的轉(zhuǎn)移,。
腫瘤的轉(zhuǎn)移難以預(yù)測(cè),，治療更難,。新發(fā)現(xiàn)為研究人員提供了關(guān)鍵線索，以深入理解癌細(xì)胞如何在距離原發(fā)腫瘤遙遠(yuǎn)的地方建立“第二戰(zhàn)場(chǎng)”,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature Cell Biology,，10, 1349 - 1355，Sachie Hiratsuka,，Yoshiro Maru
The S100A8–serum amyloid A3–TLR4 paracrine cascade establishes a pre-metastatic phase
Sachie Hiratsuka1, Akira Watanabe2, Yoshiko Sakurai1, Sachiko Akashi-Takamura3, Sachie Ishibashi1, Kensuke Miyake3, Masabumi Shibuya4, Shizuo Akira5, Hiroyuki Aburatani2 & Yoshiro Maru1
A large number of macrophages and haematopoietic progenitor cells accumulate in pre-metastatic lungs1, 2 in which chemoattractants, such as S100A8 and S100A9, are produced by distant primary tumours serving as metastatic soil3. The exact mechanism by which these chemoattractants elicit cell accumulation is not known. Here, we show that serum amyloid A (SAA) 3, which is induced in pre-metastatic lungs by S100A8 and S100A9, has a role in the accumulation of myeloid cells and acts as a positive-feedback regulator for chemoattractant secretion. We also show that in lung endothelial cells and macrophages, Toll-like receptor (TLR) 4 acts as a functional receptor for SAA3 in the pre-metastatic phase. In our study, SAA3 stimulated NF-B signalling in a TLR4-dependent manner and facilitated metastasis. This inflammation-like state accelerated the migration of primary tumour cells to lung tissues, but this was suppressed by the inhibition of either TLR4 or SAA3. Thus, blocking SAA3–TLR4 function in the pre-metastatic phase could prove to be an effective strategy for the prevention of pulmonary metastasis.
1 Department of Pharmacology, Tokyo Women's Medical University School of Medicine, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
2 Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8904, Japan.
3 Division of Infectious Genetics, Department of Microbiology and immunology, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
4 Division of Genetics, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
5 Department of Host Defense, Research Institute for Microbial Disease, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-1871, Japan.
