Extracellular ATP drives breast cancer cell migration and metastasis via S100A4 production by cancer cells and fibroblasts
Extracellular ATP drives breast cancer cell migration and metastasis via S100A4 production by cancer cells and fibroblasts
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细胞外 ATP 通过癌细胞和成纤维细胞产生 S100A4 驱动乳腺癌细胞迁移和转移
DOI：
10.1016/j.canlet.2018.04.043
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发表时间：
2018-01-01
期刊：
影响因子：
9.7
通讯作者：
Fang, Wei-Gang
中科院分区：
文献类型：
--
作者：
Liu, Ying;Geng, Yue-Hang;Fang, Wei-Gang
我们以前的工作已经证明，细胞外ATP是一个重要的促侵袭因子，在这项研究中，我们挖掘了一个可能的机制。我们发现，在？可上调乳腺癌细胞和成纤维细胞中S100A4的细胞内表达和分泌。除了通过细胞内S100A4刺激乳腺癌细胞运动外，ATP还增强了乳腺癌细胞将成纤维细胞转化为癌症相关成纤维细胞（CAF）样细胞的能力，后者进而分泌S100A4以进一步促进癌细胞运动。腺苷三磷酸双磷酸酶和氯硝柳胺处理可以抑制小鼠模型中接种的肿瘤向肺、肝和肾的转移，并且来自这些处理过的肿瘤的CAFs表现出对乳腺癌细胞的迁移刺激能力减弱。总的来说，我们的数据表明，细胞外ATP促进乳腺癌细胞和成纤维细胞之间的相互作用，它们通过产生S100A4协同工作，加剧乳腺癌转移。
Our previous work has demonstrated that extracellular ATP is an important pro-invasive factor, and in this study, we tapped into a possible mechanism involved. We discovered that AT? could upregulate both the intracellular expression and secretion of S100A4 in breast cancer cells and fibroblasts. Apart from stimulating breast cancer cell motility via intracellular S100A4, ATP enhanced the ability of breast cancer cells to transform fibroblasts into cancer-associated fibroblast (CAF)-like cells, which in turn secreted S100A4 to further promote cancer cell motility. Both apyrase and niclosamide treatments could inhibit metastasis of inoculated tumors to lung, liver and kidney in mice model, and CAFs from these treated tumors exhibited weakened migration stimulating capacity for breast cancer cells. Collectively, our data indicate that extracellular ATP promotes the interactions between breast cancer cells and fibroblasts, which work collaboratively via production of S100A4 to exacerbate breast cancer metastasis.