Upregulation of S100A10 in metastasized breast cancer stem cells. Issue 12 (11th October 2020)

• Record Type: Journal Article
• Authors: Yanagi, Hisano; Watanabe, Takashi; Nishimura, Tatsunori; Hayashi, Takanori; Kono, Seishi; Tsuchida, Hitomi; Hirata, Munetsugu; Kijima, Yuko; Takao, Shintaro; Okada, Seiji; Suzuki, Motoshi; Imaizumi, Kazuyoshi; Kawada, Kenji; Minami, Hironobu; Gotoh, Noriko; Shimono, Yohei
• Is Part Of: Cancer science. Volume 111:Issue 12(2020)
• Page Start: 4359
• Page End: 4370
• Publication Date: 2020-10-11
• Subjects: breast cancer -- cancer stem cells -- metastasis -- patient‐derived tumor xenograft -- S100A10; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.14659
• Languages: English
• ISSNs: 1347-9032

Abstract

Abstract: Metastatic progression remains the major cause of death in human breast cancer. Cancer cells with cancer stem cell (CSC) properties drive initiation and growth of metastases at distant sites. We have previously established the breast cancer patient‐derived tumor xenograft (PDX) mouse model in which CSC marker CD44 + cancer cells formed spontaneous microscopic metastases in the liver. In this PDX mouse, the expression levels of S100A10 and its family proteins were much higher in the CD44 + cancer cells metastasized to the liver than those at the primary site. Knockdown of S100A10 in breast cancer cells suppressed and overexpression of S100A10 in breast cancer PDX cells enhanced their invasion abilities and 3D organoid formation capacities in vitro. Mechanistically, S100A10 regulated the matrix metalloproteinase activity and the expression levels of stem cell–related genes. Finally, constitutive knockdown of S100A10 significantly reduced their metastatic ability to the liver in vivo. These findings suggest that S100A10 functions as a metastasis promoter of breast CSCs by conferring both invasion ability and CSC properties in breast cancers. Abstract : Members of the S100 protein family, including S100A10, were highly upregulated in metastasized cancer stem cells (CSCs) compared with primary CSCs. Among them, S100A10 functioned as an enhancer of both CSC properties and invasion abilities, and its knockdown suppressed liver metastases in a mouse xenograft model.