Effect of Bj-PRO-10c on exosomal miRNA expression: role in cancer cachexia and neuroblastoma metastasis

Abstract

Neuroblastoma, an important cause of mortality in pediatric oncology, presents as metastatic disease in approximately 50% of patients. The relation of NO (nitric oxide) with the neuroblastoma progression has been studied in our laboratory LEM³ (Laboratory of Study of Molecular Mechanisms of Metastasis). We found that NO induced by Bj-PRO-10c, a peptide from Bothrops jararaca venom, imparts an antiproliferative and adhesion inducing effect on neuroblastoma cells, in addition to blocking the formation of actin filaments, which is extremely important for reorganization of the cytoskeleton and, consequently, tumor migration and invasion. Furthermore, in a neuroblastoma xenograft model, we verified that mice receiving Bj-PRO-10c treated tumors had a delay in tumor growth and prevented the establishment of cachexia in the animals. Thus, our data have shown the great potential of Bj-PRO-10c as an anti-metastatic and anticachetic agent. Therefore, this project proposes the investigation of the role of extracellular vesicles released by neuroblastoma cells under the treatment of Bj-PRO-10c in both metastasis and cancer cachexia, since the signaling cascades via exosomes in the regulation of physiological processes and the promotion of diseases such as cancer has long been studied. In this way, the goal of the project, in collaboration with Professor Pranela Rameshwar of the New Rutgers Medical School in New Jersey, is to study the exosomes released by Bj-PRO-10c-treated neuroblastoma cells and bring the methodology of exosome study to the LEM3. (AU)