Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/102787
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Type: Journal article
Title: Desmoglein 2 promotes vasculogenic mimicry in melanoma and is associated with poor clinical outcome
Author: Tan, L.
Mintoff, C.
Johan, M.
Ebert, B.
Fedele, C.
Zhang, Y.
Szeto, P.
Sheppard, K.
McArthur, G.
Foster-Smith, E.
Ruszkiewicz, A.
Brown, M.
Bonder, C.
Shackleton, M.
Ebert, L.
Citation: Oncotarget, 2016; 7(29):46492-46508
Publisher: Impact journals
Issue Date: 2016
ISSN: 1949-2553
1949-2553
Statement of
Responsibility: 
Lih Yin Tan, Chris Mintoff, M. Zahied Johan, Brenton W. Ebert, Clare Fedele, You Fang Zhang, Pacman Szeto, Karen E. Sheppard, Grant A. McArthur, Erwin Foster-Smith, Andrew Ruszkiewicz, Michael P. Brown, Claudine S. Bonder, Mark Shackleton, Lisa M. Ebert
Abstract: Tumors can develop a blood supply not only by promoting angiogenesis but also by forming vessel-like structures directly from tumor cells, known as vasculogenic mimicry (VM). Understanding mechanisms that regulate VM is important, as these might be exploitable to inhibit tumor progression. Here, we reveal the adhesion molecule desmoglein 2 (DSG2) as a novel mediator of VM in melanoma. Analysis of patient-derived melanoma cell lines and tumor tissues, and interrogation of The Cancer Genome Atlas (TCGA) data, revealed that DSG2 is frequently overexpressed in primary and metastatic melanomas compared to normal melanocytes. Notably, this overexpression was associated with poor clinical outcome. DSG2+ melanoma cells self-organized into tube-like structures on Matrigel, indicative of VM activity, which was inhibited by DSG2 knockdown or treatment with a DSG2-blocking peptide. Mechanistic studies revealed that DSG2 regulates adhesion and cell-cell interactions during tube formation, but does not control melanoma cell viability, proliferation or motility. Finally, analysis of patient tumors revealed a correlation between DSG2 expression, VM network density and expression of VM-associated genes. These studies identify DSG2 as a key regulator of VM activity in human melanoma and suggest this molecule might be therapeutically targeted to reduce tumor blood supply and metastatic spread.
Keywords: melanoma; desmoglein 2; vasculogenic mimicry; cadherin, TCGA
Rights: © All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
RMID: 0030055653
DOI: 10.18632/oncotarget.10216
Grant ID: http://purl.org/au-research/grants/nhmrc/1053792
http://purl.org/au-research/grants/nhmrc/1022150
http://purl.org/au-research/grants/nhmrc/1002654
http://purl.org/au-research/grants/nhmrc/1106576
Appears in Collections:Medicine publications

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