マル　ヨシロウ   Maru Yoshiro   丸　義朗    所属   医学部 医学科    職種   教授・基幹分野長
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	The S100A8-serum amyloid A3-TLR4 paracrine cascade establishes a pre-metastatic phase.
掲載誌名	正式名：Nature cell biology 略　 称：Nat Cell Biol ISSNコード：(1476-4679)1465-7392(Linking)
掲載区分	国外
巻・号・頁	10(11),pp.1349-55
著者・共著者	Hiratsuka Sachie, Watanabe Akira, Sakurai Yoshiko, Akashi-Takamura Sachiko, Ishibashi Sachie, Miyake Kensuke, Shibuya Masabumi, Akira Shizuo, Aburatani Hiroyuki, Maru Yoshiro
担当区分	最終著者,責任著者
発行年月	2008/11
概要	A large number of macrophages and haematopoietic progenitor cells accumulate in pre-metastatic lungs in which chemoattractants, such as S100A8 and S100A9, are produced by distant primary tumours serving as metastatic soil. 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-kappaB 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.
DOI	10.1038/ncb1794
PMID	18820689