Upregulation of S100A10 in metastasized breast cancer stem cells

• Published in: Cancer science Vol. 111; no. 12; pp. 4359 - 4370
• Main 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
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.12.2020; John Wiley and Sons Inc
• Subjects: Animals; Annexin A2 - genetics; Annexin A2 - metabolism; Antibodies; Binding sites; Breast cancer; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Calcium-binding protein; Cancer; cancer stem cells; Care and treatment; CD44 antigen; Cell Line, Tumor; Cloning; Deoxyribonucleic acid; Disease Progression; DNA; Female; Gene expression; Gene Expression Profiling; Gene Knockout Techniques; Genes; Humans; Hyaluronan Receptors - metabolism; Lentivirus - genetics; Liver; Liver Neoplasms - pathology; Liver Neoplasms - secondary; Matrix metalloproteinase; Matrix Metalloproteinases - metabolism; Metalloproteinase; Metastases; Metastasis; Mice; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplastic Stem Cells - metabolism; Neoplastic Stem Cells - pathology; Organoids; Original; patient‐derived tumor xenograft; Proteins; Reverse Transcriptase Polymerase Chain Reaction; S100 protein; S100 Proteins - genetics; S100 Proteins - metabolism; S100A10; Stem cell transplantation; Stem cells; Tumors; Up-Regulation; Xenografts; patient-derived tumor xenograft; breast cancer; cancer stem cells; metastasis; S100A10
• ISSN: 1347-9032; 1349-7006; 1349-7006
• DOI: 10.1111/cas.14659

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. 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.