Image of the research group. (Photo DICYT)
Tumor cells with high aggressiveness are able to acquire characteristics of vascular cells (endothelial cells) 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 Cancer (CIBERONC), led by Javier Oliver, have published a report in Cell Death and Differentiation, it addresses the following question: How can they convert a metastatic cell into a ‘false endothelial cell’?
According to the researchers, this mechanism by which cancer cells “disguise themselves” responds to a property called vasculogenic mimicry (VM). In this regard, Javier Oliver, group leader of CIBERONC and CSIC researcher at the López Neyra Institute of Granada, explains that “tumors that present this mimicry have a poor prognosis and resistance to antitumor therapy, hence the interest we have in knowing the changes that the tumor cells have to undergo to become a pseudo-endothelium.
“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 also define a new therapeutic target to avoid this transformation and the acquisition of metastatic characteristics through of 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 of our work, their use could benefit a greater number of patients and a more adverse clinical situation,” concludes the researcher of the CIBERONC and CSIC Javier Oliver.
Sources: (CIBER / CSIC / DICYT) and (NCYT® (Noticiasdelaciencia.com / Amazings.com). https://noticiasdelaciencia.com/art/33093/descubren-como-se-disfraza-una-celula-tumoral-de-una-vascular-in-the-tipos-de-cancer-mas-agresivos