Abety, Anna N., Fox, Jay W., Schoenefuss, Alexander, Zamek, Jan, Landsberg, Jenny, Krieg, Thomas, Blobel, Carl, Mauch, Cornelia and Zigrino, Paola ORCID: 0000-0002-7470-0064 (2012). Stromal Fibroblast-Specific Expression of ADAM-9 Modulates Proliferation and Apoptosis in Melanoma Cells In Vitro and In Vivo. J. Invest. Dermatol., 132 (10). S. 2451 - 2459. NEW YORK: NATURE PUBLISHING GROUP. ISSN 0022-202X

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Abstract

ADAMs are members of the zinc metalloproteinase superfamily characterized by the presence of disintegrin and metalloprotease domains. In human melanoma, ADAM-9 is expressed in focalized areas of the tumor-stroma border in both melanoma and stromal cells. However, the role of ADAM-9 in melanoma progression remains elusive. To analyze the role of stromal-derived ADAM-9 for the growth and survival of melanoma cells, we have used in vitro coculture systems of melanoma cells and ADAM-9(-/-) fibroblasts. Coculture of melanoma cells in the presence of ADAM-9(-/-) fibroblasts led to increased melanoma cell proliferation and reduced apoptosis as compared with control cocultures. We identified TIMP-1 and sTNFRI as the two relevant factors expressed in increased amounts in culture supernatants from ADAM-9(-/-) fibroblasts. TIMP-1 was associated with induced melanoma cell proliferation, whereas soluble TNFR1 mediated the reduced cellular apoptosis in vitro. In vivo, injection of murine melanoma cells into the flank of ADAM-9(-/-) animals resulted in the development of significantly larger tumors than in wild-type animals as a result of increased proliferation and decreased apoptosis of melanoma cells. Taken together, stromal expression of ADAM-9 during melanoma development modulates the expression of TIMP-1 and sTNFR1, which in turn affect tumor cell proliferation and apoptosis.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Abety, Anna N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fox, Jay W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schoenefuss, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zamek, JanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Landsberg, JennyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krieg, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blobel, CarlUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mauch, CorneliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zigrino, PaolaUNSPECIFIEDorcid.org/0000-0002-7470-0064UNSPECIFIED
URN: urn:nbn:de:hbz:38-482175
DOI: 10.1038/jid.2012.153
Journal or Publication Title: J. Invest. Dermatol.
Volume: 132
Number: 10
Page Range: S. 2451 - 2459
Date: 2012
Publisher: NATURE PUBLISHING GROUP
Place of Publication: NEW YORK
ISSN: 0022-202X
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
TISSUE INHIBITOR; TNF-ALPHA; TUMOR; CANCER; INVASION; MICE; METALLOPROTEINASES-1; DISINTEGRIN; PROGRESSION; PROTEASESMultiple languages
DermatologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/48217

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