Upregulation of S100A10 in metastasized breast cancer stem cells

Autor: Hironobu Minami, Kenji Kawada, Yohei Shimono, Takashi Watanabe, Seiji Okada, Takanori Hayashi, Tatsunori Nishimura, Hisano Yanagi, Seishi Kono, Shintaro Takao, Motoshi Suzuki, Kazuyoshi Imaizumi, Hitomi Tsuchida, Munetsugu Hirata, Noriko Gotoh, Yuko Kijima
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
cancer stem cells
Cancer Research
Metastasis
Gene Knockout Techniques
Mice
0302 clinical medicine
Cell
Molecular
and Stem Cell Biology
Neoplasm Metastasis
Annexin A2
Gene knockdown
Reverse Transcriptase Polymerase Chain Reaction
Liver Neoplasms
S100 Proteins
General Medicine
Up-Regulation
Organoids
Hyaluronan Receptors
Oncology
030220 oncology & carcinogenesis
Disease Progression
Neoplastic Stem Cells
Original Article
Female
Stem cell
Breast Neoplasms
Biology
03 medical and health sciences
Breast cancer
breast cancer
Cancer stem cell
Cell Line
Tumor
medicine
Animals
Humans
metastasis
Neoplasm Invasiveness
patient‐derived tumor xenograft
Gene Expression Profiling
CD44
Lentivirus
Cancer
Original Articles
medicine.disease
patient-derived tumor xenograft
Matrix Metalloproteinases
030104 developmental biology
Cancer cell
S100A10
Cancer research
biology.protein
Zdroj: Cancer Science
ISSN: 1347-9032
Popis: 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.
Databáze: OpenAIRE
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