Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China; Department of Pathology, Peking University Third Hospital, Beijing, 100191, China.
Department of Pathology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.
Cancer Lett. 2018 Aug 28;430:1-10. doi: 10.1016/j.canlet.2018.04.043. Epub 2018 May 5.
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 ATP 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.
我们之前的工作已经证明细胞外 ATP 是一种重要的促侵袭因子，在这项研究中，我们探讨了可能涉及的一种机制。我们发现 ATP 可以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 刺激乳腺癌细胞的运动性，ATP 还增强了乳腺癌细胞将成纤维细胞转化为癌相关成纤维细胞（CAF）样细胞的能力，而这些 CAF 则分泌 S100A4 进一步促进了癌细胞的运动性。使用 apyrase 和 niclosamide 处理可以抑制接种肿瘤在小鼠模型中向肺、肝和肾的转移，并且来自这些处理过的肿瘤的 CAFs 对乳腺癌细胞的迁移刺激能力减弱。总之，我们的数据表明细胞外 ATP 促进了乳腺癌细胞和成纤维细胞之间的相互作用，通过 S100A4 的产生协同作用，加剧了乳腺癌的转移。
