Active Secretion of Dimerized S100A11 Induced by the Peroxisome in Mesothelioma Cells

• Published in: Cancer microenvironment Vol. 9; no. 2-3; pp. 93 - 105
• Main Authors: Saho, Satomi, Satoh, Hiroki, Kondo, Eisaku, Inoue, Yusuke, Yamauchi, Akira, Murata, Hitoshi, Kinoshita, Rie, Yamamoto, Ken-ichi, Futami, Junichiro, Putranto, Endy Widya, Ruma, I Made Winarsa, Sumardika, I Wayan, Youyi, Chen, Suzawa, Ken, Yamamoto, Hiromasa, Soh, Junichi, Tomida, Shuta, Sakaguchi, Yoshihiko, Saito, Ken, iioka, Hidekazu, Huh, Nam-ho, Toyooka, Shinichi, Sakaguchi, Masakiyo
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.12.2016
• Subjects: Biochemistry; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cell Biology; Immunology; Oncology; Original; Original Article; Peroxisome; Mesothelioma; Metastasis; Tumor microenvironment; S100A11; Lysosome
• ISSN: 1875-2292; 1875-2284
• DOI: 10.1007/s12307-016-0185-2

S100A11, a small Ca 2+ binding protein, acts extracellularly as a mediator of cancer progression. That raises the question of how a protein that lacks the classical secretory signal is able to be secreted outside cells without being damaged. Some insights into this question have been obtained, and there has been accumulating evidence indicating a pivotal role of a non-classical vesicle-mediated pathway using lysosomes or peroxisomes for the protein secretion. To obtain a more precise insight into the secretory mechanism of S100A11, we first screened representative cancer cells exhibiting significantly active secretion of S100A11. From the results of profiling, we turned our attention to aggressive cancer mesothelioma cells. In mesothelioma cells, we found that abundant dimeric S100A11 was produced selectively in the peroxisome after transportation of monomeric S100A11 through an interaction with PEX14, a peroxisome membrane protein, resulting in peroxisomal secretion of dimerized S100A11. In an extracellular environment in vitro, dimerized S100A11 promoted mesothelial cell invasion indirectly with the help of fibroblast cells. Overall, the results indicate that the peroxisome functions as an essential vesicle for the production of dimerized S100A11 and the subsequent secretion of the protein from mesothelioma cells and that peroxisome-mediated secretion of dimerized S100A11 might play a critical role in mesothelioma progression in a tumor microenvironment.