Advanced SearchSearch Tips
The ADAM15 ectodomain is shed from secretory exosomes
facebook(new window)  Pirnt(new window) E-mail(new window) Excel Download
  • Journal title : BMB Reports
  • Volume 48, Issue 5,  2015, pp.277-282
  • Publisher : Korean Society for Biochemistry and Molecular Biology
  • DOI : 10.5483/BMBRep.2015.48.5.161
 Title & Authors
The ADAM15 ectodomain is shed from secretory exosomes
Lee, Hee Doo; Kim, Yeon Hyang; Koo, Bon-Hun; Kim, Doo-Sik;
  PDF(new window)
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]
ADAM15;Ectodomain shedding;Exosomes;MEK/ERK signaling;Tumor suppression;
 Cited by
Influence of Storage Condition on Exosome Recovery,;;;;

Biotechnology and Bioprocess Engineering:BBE, 2016. vol.21. 2, pp.299-304 crossref(new window)
Glycosyl-Phosphatidyl-Inositol (GPI)-Anchors and Metalloproteases: Their Roles in the Regulation of Exosome Composition and NKG2D-Mediated Immune Recognition, Frontiers in Cell and Developmental Biology, 2016, 4  crossref(new windwow)
The emerging roles and therapeutic potential of exosomes in epithelial ovarian cancer, Molecular Cancer, 2017, 16, 1  crossref(new windwow)
Exosomes from adipose-derived stem cells ameliorate phenotype of Huntington's diseasein vitromodel, European Journal of Neuroscience, 2016, 44, 4, 2114  crossref(new windwow)
ADAM9 is present at endothelial cell - cell junctions and regulates monocyte – endothelial transmigration, Biochemical and Biophysical Research Communications, 2017  crossref(new windwow)
Influence of storage condition on exosome recovery, Biotechnology and Bioprocess Engineering, 2016, 21, 2, 299  crossref(new windwow)
SheddomeDB: the ectodomain shedding database for membrane-bound shed markers, BMC Bioinformatics, 2017, 18, S3  crossref(new windwow)
Adipose-derived stem cell exosomes alleviate pathology of amyotrophic lateral sclerosis in vitro, Biochemical and Biophysical Research Communications, 2016, 479, 3, 434  crossref(new windwow)
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 crossref(new window)

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 crossref(new window)

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 crossref(new window)

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 crossref(new window)

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 crossref(new window)

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 crossref(new window)

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 crossref(new window)

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 crossref(new window)

Cocucci E, Racchetti G and Meldolesi J (2009) Shedding microvesicles: artefacts no more. Trends Cell Biol 19, 43-51 crossref(new window)

Thery C, Ostrowski M and Segura E (2009) Membrane vesicles as conveyors of immune responses. Nat Rev Immunol 9, 581-593 crossref(new window)

Mathivanan S and Simpson RJ (2009) ExoCarta: A compendium of exosomal proteins and RNA. Proteomics 9, 4997-5000 crossref(new window)

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 crossref(new window)

Weber S and Saftig P (2012) Ectodomain shedding and ADAMs in development. Development 139, 3693-3709 crossref(new window)

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

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 crossref(new window)

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 crossref(new window)

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 crossref(new window)

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 crossref(new window)

Keller S, Sanderson MP, Stoeck A and Altevogt P (2006) Exosomes: from biogenesis and secretion to biological function. Immunology Lett 107, 102-108 crossref(new window)

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 crossref(new window)

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 crossref(new window)

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 crossref(new window)