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Cancer Lett. 2018 Aug 28;430:1-10. doi: 10.1016/j.canlet.2018.04.043. Epub 2018 May 5.

Extracellular ATP drives breast cancer cell migration and metastasis via S100A4 production by cancer cells and fibroblasts.

Author information

1
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.
2
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.
3
Department of Anatomy, Histology and Embryology, Peking University Health Science Center, Beijing, 100191, China.
4
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. Electronic address: tianxinxia@163.com.
5
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. Electronic address: wgfang@bjmu.edu.cn.

Abstract

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.

KEYWORDS:

Breast cancer metastasis; Extracellular ATP; Fibroblast; S100A4; Tumor microenvironment

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