Portal de Murcia

www.portaldemurcia.com

• Home
• Business
• Hotels
• Restaurants
• News
• Advertisement

The finding, led by the researcher at the University of Murcia (UMU) Rut Valdor, opens the possibility to new therapies oriented to the cells (perivascular) that surround the small blood vessels of the brain known as pericytes and which are the main causes of inadequate response of the immune system to glioblastoma.

Through this study, published in PNAS, it is proven that the pericito's immune function changes when it interacts with the glioblastoma cell through chaperone-mediated autophagy.

When this interaction occurs, the pericyte, "instead of favoring the elimination of tumor cells, is stunned and sleepy, does not proliferate and, in addition, secretes factors that paralyze the response to the tumor cell and, therefore, allows the tumor grows and spreads, "Valdor explains.

This mechanism is modulated by the brain tumor for its own benefit, not only in the tumor cell itself, as previously seen in other cancers, but also in the parasitized cell (the pericyte), which is responsible for survival and growth. of the tumor through an appropriate physical interaction to obtain nutrients and factors that favor the tumor.

All this allows the results obtained to serve not only for brain tumors, but could be extrapolated to other types of tumors.

The importance of this study is that when this type of autophagy is blocked there is a change in the levels of protein involved in the interaction of tumor cells-perivascular cells and the pericyte responds effectively as a defense cell alerting the rest of the immune system, the which reacts correctly favoring the removal of the tumor.

As the researcher points out, in normal conditions, in a healthy brain, "the pericytes have, among others, an immune defense function eliminating toxic molecules and activating inflammatory factors that allow the immune system to eliminate, for example, bacterial or virus infections. ".

This procedure, which has already been tested in a rodent model to reverse the tumor process, opens an important way to create future treatments for glioblastoma.

In addition, the study has been confirmed in biopsies of patients with glioblastoma tumor.

The study, which is in a preclinical phase and that has new funding received from the Seneca Foundation of the Region of Murcia to continue the project, has been developed in collaboration with the Instituto Virgenno de Biosanitaria Research Virgen de la Arrixaca (IMIB ) of the UMU, the Institute of Neuroscience of Alicante and two prestigious laboratories of the Albert Einstein Collegue of Medicine in New York: that of Doctor Fernando Macian and that of Dr. Ana María Cuervo, who were the chiefs and mentors of Valdor during their stay In U.S.A.

Chaperone-mediated autophagy, a mechanism that allows tumor survival

The research reveals "a previously unknown ability of the brain tumor to modulate the proteins that regulate an effective immune response against the tumor in the pericytes through chaperone-mediated autophagy. It is a specific protein degradation mechanism that is highly deregulated. and it degrades these proteins in such a massive way that it distorts the defense functions against the tumor, helping it in its own progression, "says the researcher.

This process, therefore, is to blame for a change in the function of the parakeets, which go from being defense cells to becoming 'enemies'.

Chaperone-mediated autophagy regulates the interaction of pericytes with tumor cells and maintains the immunosuppressive function and anti-inflammatory phenotype acquired by the pericytes, and in turn required for tumor survival.

It is, therefore, through the interaction between tumor cells and pericytes that these perivascular cells go from acting as tumor suppressors to promoting it.

The tumor also, through chaperone-mediated autophagy, parasites the pericyte, using its nutrients and secreted factors for its own benefit.

The key: block the interaction

The results obtained show that by blocking chaperone-mediated autophagy selectively through the only protein that limits this process, LAMP-2A, and as a possible and promising therapeutic target, pericytes are prevented from interfering with the natural process that these cells would develop as a defense of the brain

In this way, the survival of the tumor decreases "by preventing the tumor cells from interacting with the pericytes, preventing the tumor cell from modifying the immune function of defense of the pericyte and nourishing it, allowing the rest of the immune system to function properly and react against the tumor, "Valdor explains.

A joint project

Rut Valdor is part of the Research Group of Hematology, Hematopoietic Transplantation and Cell Therapy of the UMU, multidisciplinary, formed by basic and clinical researchers and led by Dr. José María Moraleda.

In addition, he collaborates strongly with the Brain Regionalization and Development Genes Group of IMIB-Arrixaca and with Dr. Salvador Martínez, director of the Neurosciences Institute, Miguel Hernández University.

This research, funded through the call of young researchers from the Ministry of Economy and Competitiveness (MINECO), has its origins in the Albert Einstein College of Medicine in New York, where Valdor spent five years of postdoctoral training.

After returning he joined as a postdoctoral in the line of research on progression of glioblastoma and pericytes, from the group of Dr. Martínez, then director of IMIB-Arrixaca.

He returned 6 months back to New York, through a grant from the Seneca Foundation ("Jimenez de la Espada Program", 19667 / EE / 14) to obtain what would be the preliminary and promising results on the molecular mechanism of autophagy

This is her first job as Principal Investigator in which she is the only author of correspondence, in addition to the first author, which translates into being responsible leader and coordinator of the study among the different institutions that have collaborated.

In addition, he has designed the study, as well as carried out most of the experiments.

This work of great effort and dedication has been the main result of a project that was granted to seek "scientific stability and consolidate in the face of an uncertain future."

Source: Universidad de Murcia