研究人员在日前在线出版的《自然—细胞生物学》期刊上报告说，肿瘤转移细胞利用一种机制侵入肺部，并在那里建立起次生肿瘤。新研究鉴别出一种有潜力的药物靶标，可以预防癌症的扩散。
趋化因子是一种化学因子，其功能是在感染发生时征集免疫细胞。科学家们发现，原发肿瘤通过引入趋化因子为入侵肺部作准备，这时趋化因子的作用是指引肿瘤细胞进入“第二战场”。Hiratsuka和同事指出，与此同时，原发肿瘤也诱导肺细胞产生一种名为血清淀粉样蛋白A3(SAA3)附加因子。通过启动与炎症有关的一种基因，SAA3加速了原发肿瘤细胞的征集，促进了趋化因子的产出。重要的是，Hiratsuka研究小组发现，阻断SAA3或其受体能降低小鼠肺部肿瘤的转移。
肿瘤的转移难以预测，治疗更难。新发现为研究人员提供了关键线索，以深入理解癌细胞如何在距离原发肿瘤遥远的地方建立“第二战场”。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
