Abstract
Abstract S100A14 is a member of S100 calcium-binding protein family. Our previous studies have reported that S100A14 modulates a variety of tumorigenic processes by functioning both as intracellular and extracellular factors. Emerging evidence indicated that the biology of most S100 proteins is complex and multifactorial. Herein, we identify S100A14 is upregulated in Lymph Node (LN) metastasis breast cancer (BC) and associated with LN metastasis and prognosis. Through gain and loss of function approaches, we find that S100A14 promotes cell migratory and invasive capabilities in vitro and lung metastasis in vivo. More convincingly, S100A14 knockout also suppresses the lung metastases without affecting the primary tumor growth in MMTV-PyMT mouse models. Using a combination of iTRAQ based quantitative proteomics and transcriptomics, we identified CCL2 as a downstream target of S100A14. Importantly, systemic delivery of anti-CCL2 antibody significantly inhibited S100A14-enhanced cell migration and invasion, tumor-associated macrophages (TAMs) accumulation and lung metastasis. Finally, we indicated that the increased serum S100A14 levels could be used for the detection of BC and the prediction of LN metastases. These findings provide a plausible mechanism for S100A14-modulated tumor microenvironment in metastasis and show that S100A14-mediated CCL2 signaling plays a prominent role in breast cancer metastasis, which may have clinical implications for providing novel biomarkers and potential therapeutic targets of breast cancer in future. Note: This abstract was not presented at the meeting. Citation Format: Hongyan Chen, Xukun Li, Zhihua Liu. S100A14 promotes breast cancer metastasis via CCL2 dependent macrophage recruitment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-126.
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