Tumour-mediated upregulation of chemoattractants and recruitment of myeloid cells predetermines lung metastasis
Tumour-mediated upregulation of chemoattractants and recruitment of myeloid cells predetermines lung metastasis
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DOI：
10.1038/ncb1507
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发表时间：
2006-12-01
影响因子：
21.3
通讯作者：
Maru, Yoshiro
中科院分区：
文献类型：
--
作者：
Hiratsuka, Sachie;Watanabe, Akira;Maru, Yoshiro
原发性肿瘤在转移之前影响肺中的环境（1，2）。然而，转移的机制还不清楚。在这里，我们表明，炎症化学引诱物S100 A8和S100 A9，其表达是由远处原发肿瘤诱导，吸引Mac 1（巨噬细胞抗原1）（+）-髓样细胞在转移前肺。此外，肿瘤细胞利用这种机制，通过激活促分裂原活化蛋白激酶（MAPK）p38，以获得具有伪足的迁移活性，用于侵袭（侵袭伪足）。S100 A8和S100 A9的表达在去除可溶性因子如血管内皮生长因子A（VEGF-A）、肿瘤坏死因子α（TNF α）和转化生长因子β（TGF β）的肺Mac 1（+）-髓样细胞和内皮细胞中在体外和体内均被消除。中和抗S100 A8和抗S100 A9抗体阻断肿瘤细胞和Mac 1+-骨髓细胞的形态学变化和迁移。因此，S100 A8和S100 A9通路可能是骨髓细胞募集和肿瘤细胞侵袭所共有的。
Primary tumours influence the environment in the lungs before metastasis(1,2). However, the mechanism of metastasis is not well understood. Here, we show that the inflammatory chemoattractants S100A8 and S100A9, whose expression is induced by distant primary tumours, attract Mac 1 (macrophage antigen 1)(+)-myeloid cells in the premetastatic lung. In addition, tumour cells use this mechanism, through activation of the mitogen-activated protein kinase (MAPK) p38, to acquire migration activity with pseudopodia for invasion (invadopodia). The expression of S100A8 and S100A9 was eliminated in lung Mac 1(+)-myeloid cells and endothelial cells deprived of soluble factors, such as vascular endothelial growth factor A (VEGF-A), tumour necrosis factor a (TNF alpha) and transforming growth factor beta (TGF beta) both in vitro and in vivo. Neutralizing anti-S100A8 and anti-S100A9 antibodies blocked the morphological changes and migration of tumour cells and Mac 1+-myeloid cells. Thus, the S100A8 and S100A9 pathway may be common to both myeloid cell recruitment and tumour-cell invasion.