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Maru Yoshiro
Department School of Medicine, School of Medicine Position Professor and Division head |
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| Article types | Original article |
| Language | English |
| Peer review | Peer reviewed |
| Title | The S100A8-serum amyloid A3-TLR4 paracrine cascade establishes a pre-metastatic phase. |
| Journal | Formal name：Nature cell biology Abbreviation：Nat Cell Biol ISSN code：(1476-4679)1465-7392(Linking) |
| Domestic / Foregin | Foregin |
| Volume, Issue, Page | 10(11),pp.1349-55 |
| Author and coauthor | Hiratsuka Sachie, Watanabe Akira, Sakurai Yoshiko, Akashi-Takamura Sachiko, Ishibashi Sachie, Miyake Kensuke, Shibuya Masabumi, Akira Shizuo, Aburatani Hiroyuki, Maru Yoshiro |
| Authorship | Last author,Corresponding author |
| Publication date | 2008/11 |
| Summary | 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 |