CD44 enhances tumor aggressiveness by promoting tumor cell plasticity

摘要: Aggressive tumor cells can obtain the ability to transdifferentiate into with endothelial features and thus form vasculogenic networks. This phenomenon, called mimicry (VM), is associated increased malignancy poor clinical outcome. To identify novel key molecules implicated in process of mimicry, microarray analysis was performed compare gene expression profiles aggressive (VM+) non-aggressive (VM-) derived from Ewing sarcoma breast carcinoma. We identified CD44/c-Met signaling cascade as heavily relevant for mimicry. CD44 at center this cascade, highly overexpressed tumors. Both standard isoform its splice variant CD44v6 were linked aggressiveness VM. Since VM most abundant tumors functional analyses EW7 cells. Overexpression allowed enhanced adhesion extracellular matrix ligand hyaluronic acid. also facilitated formation structures vitro, knockdown experiments repressed migration vascular network formation. From these results observation that blood lakes human tissues, we conclude increases through