Highly Aggressive and Metastatic MDA-MB-231 and Mel Z Cancer Cells Have Common Sets of Down- and Upregulated Genes During Formation of the Vasculogenic Mimicry Phenotype

Vasculogenic mimicry (VM) refers to the capacity of cancer cells from aggressive tumors to form a set of sinuses and channels that mimic normal blood vessels and lack endothelial cells. The rapid growth of a tumor leads to a deficiency in normal vessels, followed by poor oxygen and nutrient supply to tumor cells and VM induction. Understanding the mechanisms behind the development of the VM phenotype is important for the development of new anti-cancer therapies. Previous reports indicate that, during VM formation by melanoma Mel Z cells, about 2000 developmental genes undergo dramatic changes in expression. To identify genes more tightly linked to VM development, we compared the transcriptomes of Mel Z and MDA-MB-231 cells (triple-negative breast cancer cells), which also form VM. Most of the genes that change expression differ substantially between these two cell types. However, we identified 51 up- and 98 downregulated genes common to both cell lines. The non-overlapping groups of these genes are involved in regulating cell adhesion and proliferation. The group of common upregulated genes includes nine genes controlling blood vessel development and tube morphogenesis. Two genes in this group (<i>BAK1</i> and <i>SERPINE1</i>) rapidly form numerous contacts with nucleoli during VM phenotype formation. We observed that knockdown of the <i>SERPINE1</i> gene prevents the development of VM in Mel Z cells. Our data indicate that the formation of VM by aggressive cancer cells might be controlled by a special set of genes.