title: The ADAM15 ectodomain is shed from secretory exosomes.
abstract: We demonstrated previously that a disintegrin and metalloproteinase 15 (ADAM15) is released into the extracellular space as an exosomal component, and that ADAM15-rich exosomes have tumor suppressive functions. However, the suppressive mechanism of ADAM15-rich exosomes remains unclear. In this study, we show that the ADAM15 ectodomain is cleaved from released exosomes. This shedding process of the ADAM15 ectodomain was dramatically enhanced in conditioned ovarian cancer cell medium. Proteolytic cleavage was completely blocked by phenylmethylsulfonyl fluoride, indicating that a serine protease is responsible for exosomal ADAM15 shedding. Experimental evidence indicates that the ADAM15 ectodomain itself has comparable functions with those of ADAM15-rich exosomes, which effectively inhibit vitronectininduced cancer cell migration and activation of the MEK/extracellular regulated kinase signaling pathway. We present a tumor suppressive mechanism for ADAM15 exosomes and provide insight into the functional significance of exosomes that generate tumor-inhibitory factors.
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea.
authors.forename: Hee Doo
authors.initials: HD
authors.lastname: Lee
authors.affiliation: Department of Bioinformatics, Korea Polytechnics, Nonsan 320-905, Korea.
authors.forename: Yeon Hyang
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea.
authors.forename: Bon-Hun
authors.initials: BH
authors.lastname: Koo
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea.
authors.forename: Doo-Sik
authors.initials: DS
authors.lastname: Kim
mesh_terms: D051722:ADAM Proteins / Q000737:chemistry / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D055354:Exosomes / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D019096:Vitronectin / Q000037:antagonists & inhibitors / Q000502:physiology
chemical_list: D008565:Membrane Proteins; D019096:Vitronectin; D051722:ADAM Proteins; C098660:ADAM15 protein, human