Title
CD44 enhances tumor aggressiveness by promoting tumor cell plasticity CD44 enhances tumor aggressiveness by promoting tumor cell plasticity
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Publication type
article
Publication
Albany, N.Y :Impact Journals ,
Subject
Biology
Human medicine
Source (journal)
Oncotarget. - Albany, N.Y, 2010, currens
Volume/pages
6(2015) :23 , p. 19634-19646
ISSN
1949-2553
ISI
000360135300035
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Aggressive tumor cells can obtain the ability to transdifferentiate into cells with endothelial features and thus form vasculogenic networks. This phenomenon, called vasculogenic mimicry (VM), is associated with increased tumor malignancy and poor clinical outcome. To identify novel key molecules implicated in the process of vasculogenic mimicry, microarray analysis was performed to compare gene expression profiles of aggressive (VM+) and non-aggressive (VM-) cells derived from Ewing sarcoma and breast carcinoma. We identified the CD44/c-Met signaling cascade as heavily relevant for vasculogenic mimicry. CD44 was at the center of this cascade, and highly overexpressed in aggressive tumors. Both CD44 standard isoform and its splice variant CD44v6 were linked to increased aggressiveness in VM. Since VM is most abundant in Ewing sarcoma tumors functional analyses were performed in EW7 cells. Overexpression of CD44 allowed enhanced adhesion to its extracellular matrix ligand hyaluronic acid. CD44 expression also facilitated the formation of vasculogenic structures in vitro, as CD44 knockdown experiments repressed migration and vascular network formation. From these results and the observation that CD44 expression is associated with vasculogenic structures and blood lakes in human Ewing sarcoma tissues, we conclude that CD44 increases aggressiveness in tumors through the process of vasculogenic mimicry.
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Full text (open access)
https://repository.uantwerpen.be/docman/irua/f5fb0a/127806.pdf
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