Tumor cells with high aggressiveness are capable of acquiring vascular (endothelial) cell characteristics in order to “imitate” a network of vessels inside a tumor so that they can provide nutrients and oxygen in the absence of blood vessels. To study this process and its basic transformations, researchers from CIBER de Cáncer (CIBERONC), led by Javier Oliver, have carried out a work that has been published in Cell Death and Differentiation, in which the following question is addressed: what basic transformations can convert a metastatic cell into a 'false endothelial cell' ?.
According to the researchers in a statement, this mechanism by which cancer cells “disguise” responds to a property called vasculogenic mimicry (VM). In this regard, Javier Oliver, group leader of the CIBERONC and researcher of the CSIC at the López Neyra Institute in Granada, explains that “Tumors that have this mimicry have a poor prognosis and resistance to antitumor therapy, hence the interest we have in knowing the changes that tumor cells have to undergo to become pseudoendothelium”.
To explain this mechanism, this study has focused on the expression of a marker that, being exclusively endothelial, is also present in some highly aggressive tumor cells, the endothelial cadherin VE-cadherin. Contrary to what happens in endothelial cells, VE-cadherin associated with vasculogenic mimicry is modified by permanent phosphorylation through a focal adhesion kinase (FAK).
Thanks to this permanent modification VE-cad, which is associated with a protein involved in the regulation of the expression of a type of genes, migrates to the cell nucleus and allows the transcription of genes that increase the capacity of vasculogenic mimicry. According to Javier Oliver, “Through mutations in the site of phosphorylation of VE-cadherin, we demonstrate the importance of this process in the development of mimicry and, in addition, we define a new therapeutic target to avoid this transformation and the acquisition of metastatic characteristics through the inhibition of FAK kinase “.
This type of anomalous behavior has been described in very aggressive tumors including metastatic melanoma, liver cancer, ovaries and gliomas, so the FAK kinase is shown as a “promising” pharmacological target for cancer therapies because it is directly related with the progression and aggressiveness of the tumor. “Their inhibitors are already being used in clinical trials and, based on the results provided by our work, their use could benefit a greater number of patients and a more adverse clinical situation”, concludes the researcher of the CIBERONC and the CSIC Javier Oliver.