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http://dx.doi.org/10.5483/BMBRep.2015.48.5.161

The ADAM15 ectodomain is shed from secretory exosomes  

Lee, Hee Doo (Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University)
Kim, Yeon Hyang (Department of Bioinformatics, Korea Polytechnics)
Koo, Bon-Hun (Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University)
Kim, Doo-Sik (Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University)
Publication Information
BMB Reports / v.48, no.5, 2015 , pp. 277-282 More about this Journal
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. [BMB Reports 2015; 48(5): 277-282]
Keywords
ADAM15; Ectodomain shedding; Exosomes; MEK/ERK signaling; Tumor suppression;
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1 Schafer B, Gschwind A and Ullrich A (2004) Multiple G-protein-coupled receptor signals converge on the epidermal growth factor receptor to promote migration and invasion. Oncogene 23, 991-999   DOI   ScienceOn
2 Wolfsberg TG, Primakoff P, Myles DG and White JM (1995) ADAM, a novel family of membrane proteins containing A Disintegrin And Metalloprotease domain: multipotential functions in cell-cell and cell-matrix interactions. J Cell Biol 131, 275-278   DOI
3 Zhang XP, Kamata T, Yokoyama K, Puzon-McLaughlin W and Takada Y (1998) Specific interaction of the recombinant disintegrin-like domain of MDC-15 (metargidin, ADAM-15) with integrin alphavbeta3. J Biol Chem 273, 7345-7350   DOI   ScienceOn
4 Najy AJ, Day KC and Day ML (2008) The ectodomain shedding of E-cadherin by ADAM15 supports ErbB receptor activation. J Biol Chem 283, 18393-18401   DOI   ScienceOn
5 Schafer B, Marg B, Gschwind A and Ullrich A (2004) Distinct ADAM metalloproteinases regulate G protein-coupled receptor-induced cell proliferation and survival. J Biol Chem 279, 47929-47938   DOI   ScienceOn
6 Najy AJ, Day KC and Day ML (2008) ADAM15 supports prostate cancer metastasis by modulating tumor cell-endothelial cell interaction. Cancer Res 68, 1092-1099   DOI   ScienceOn
7 Hou Y, Chu M, Du FF et al (2013) Recombinant disintegrin domain of ADAM15 inhibits the proliferation and migration of Bel-7402 cells. Biochem Biophys Res Commun 435, 640-645   DOI   ScienceOn
8 Lee HD, Koo BH, Kim YH, Jeon OH and Kim DS (2012) Exosome release of ADAM15 and the functional implications of human macrophage-derived ADAM15 exosomes. FASEB J 26, 3084-3095   DOI   ScienceOn
9 Lee HD, Kim YH and Kim DS (2013) Exosomes derived from human macrophages suppress endothelial cell migration by controlling integrin trafficking. Eur J Immunol 44, 1156-1169   DOI   ScienceOn
10 Cocucci E, Racchetti G and Meldolesi J (2009) Shedding microvesicles: artefacts no more. Trends Cell Biol 19, 43-51   DOI   ScienceOn
11 Thery C, Ostrowski M and Segura E (2009) Membrane vesicles as conveyors of immune responses. Nat Rev Immunol 9, 581-593   DOI   ScienceOn
12 Mathivanan S and Simpson RJ (2009) ExoCarta: A compendium of exosomal proteins and RNA. Proteomics 9, 4997-5000   DOI   ScienceOn
13 Weber S and Saftig P (2012) Ectodomain shedding and ADAMs in development. Development 139, 3693-3709   DOI   ScienceOn
14 Nayeem N, Silletti S, Yang X et al (1999) A potential role for the plasmin(ogen) system in the posttranslational cleavage of the neural cell adhesion molecule L1. J Cell Sci 112 (Pt 24), 4739-4749
15 Thimon V, Metayer S, Belghazi M, Dacheux F, Dacheux JL and Gatti JL (2005) Shedding of the germinal angiotensin I-converting enzyme (gACE) involves a serine protease and is activated by epididymal fluid. Biol Reprod 73, 881-890   DOI   ScienceOn
16 Subramanian SV, Fitzgerald ML and Bernfield M (1997) Regulated shedding of syndecan-1 and -4 ectodomains by thrombin and growth factor receptor activation. J Biol Chem 272, 14713-14720   DOI   ScienceOn
17 Klucky B, Mueller R, Vogt I et al (2007) Kallikrein 6 induces E-cadherin shedding and promotes cell proliferation, migration, and invasion. Cancer Res 67, 8198- 8206   DOI   ScienceOn
18 Salasznyk RM, Klees RF, Hughlock MK and Plopper GE (2004) ERK signaling pathways regulate the osteogenic differentiation of human mesenchymal stem cells on collagen I and vitronectin. Cell Commun Adhes 11, 137-153   DOI   ScienceOn
19 Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ and Lotvall JO (2007) Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9, 654-65   DOI   ScienceOn
20 Keller S, Sanderson MP, Stoeck A and Altevogt P (2006) Exosomes: from biogenesis and secretion to biological function. Immunology Lett 107, 102-108   DOI   ScienceOn
21 Stoeck A, Keller S, Riedle S et al (2006) A role for exosomes in the constitutive and stimulus-induced ectodomain cleavage of L1 and CD44. Biochem J 393, 609-618   DOI   ScienceOn
22 Gutwein P, Stoeck A, Riedle S et al (2005) Cleavage of L1 in exosomes and apoptotic membrane vesicles released from ovarian carcinoma cells. Clin Cancer Res 11, 2492-2501   DOI   ScienceOn