Vasculogenic mimicry in melanoma: molecular mechanisms and clinical significance

The concept of vasculogenic mimicry (VM) was introduced to describe the unique ability of highly aggressive tumor cells to form capillary-like structures and matrix-rich patterned network in three-dimensional culture that mimic embryonic vasculogenic network. VM has been reported in several aggressive tumors including ovaries, breast, liver, lung cancer, sarcoma, glioblastoma. It is worth to note, that VM in melanocyte-originated tumors is the most studied. Although much attention has been focused on factors that stimulate or suppress vascular channel formation by tumor cells, the molecular mechanisms underlying this phenomenon remain enigmatic. This review will focus on molecular determinants and key signaling pathways involved in tumor VM. The exploration of drugs targeted at molecular signaling pathways in VM is a field of challenges and hopes. The research on VM will increase our knowledge of the molecular events causing aggressive tumor cells to gain plasticity resulting in their ability to mimic vasculature. To date, little functional data exist that show how tumor cell-lined channels contribute to the overall survival of the tumor. However, even among researches who have questioned the concept of VM as a crucial circulatory system, there is generally a consensus that the prognostic significance of PAS-positive patterns is valid.