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Vasculogenic mimicry

The main aim of research line IV is tumor cell plasticity, which may lead to the dedifferentiation of tumor cells into an endothelial cell-like phenotype. This process is also referred to as vasculogenic mimicry. Vasculogenic mimicry is the angiogenesis independent formation of a circulatory system by the tumor cells. This process is associated with an increased aggressiveness tumors. We intend to get more insight in the mechanism of vasculogenic mimicry and are interested in finding therapeutic targets for the treatment of vasculogenic mimicry containing tumors.

Vasculogenic mimicry

The formation of vasculature-like structures by tumor cells was first described in 1999 by Dr. Mary Hendrix. This process was initially characterized by the presence of matrix-rich and therefore periodic acid Schiff's reagent (PAS)-positive loops in the tumor. Later other groups described it as the presence of lakes of erythrocytes lined by tumor cells.
Tumors displaying vasculogenic mimicry have a more aggressive morphologic appearance than tumors that do not have these structures. Patient survival is much shorter in cases where tumors display vasculogenic mimicry, as has been shown in melanoma and breast cancer studies. The Hendrix-group was the first to characterize the gene expression in aggressive versus non-aggressive melanoma tumor cell lines. It was found that the aggressive melanoma cell lines express genes that are compatible with a more dedifferentiated embryonic-like phenotype.

Vasculogenic mimicry in Ewing sarcoma

Ewing sarcoma was first described by James Ewing in 1921 as an endothelioma, because of the presence of high numbers of red blood cells in the tumor tissue. It is a highly aggressive and metastatic tumor that primarily arises in adolescents and young adults. In these Ewing sarcomas we detected vasculogenic mimicry in the vast majority of the tissue samples. We developed an in vivo mouse model for vasculogenic mimicry, in which we were able to show functionality (for reference view the video-image below). In vitro some Ewing sarcoma cell lines are also able to form vessel like structures. In our recent publication in Cancer Research we suggest that VM is influenced by hypoxia/HIF1alpha. We are currently exploring the gene expression profile of vasculogenic mimicry positive tumors, in an effort to understand the mechanisms of this process.

Video-image: an intravital microscopy experiment in human EW7 Ewing sarcoma tumors in athymic mice, demonstrating blood flow in the irregularly lined vasculogenic structures.