They identify new biomarkers of patients with malignant melanoma, which could help in its diagnosis and evolution
The research group TEC16-ADVANCED THERAPIES: DIFFERENTIATION, REGENERATION AND CANCER, has studied the molecular profile of small messenger vesicles, called exosomes, produced by cancer stem cells (CMCs), which act in the process of carcinogenesis and metastasis, in the blood of patients with malignant melanoma
Research has shown that these vesicles produced by CMCs have a different molecular composition than those produced by more differentiated tumor cells. In addition, these molecules are also detectable in exosomes present in the blood, and present differences in patients with malignant melanoma with respect to healthy individuals, which makes them susceptible to being considered potential biomarkers for the diagnosis and progression of this disease.
Malignant melanoma is one of the most aggressive types of skin cancer that exists and its incidence is increasing worldwide in recent years. Among the factors that contribute to the lethality and severity of this disease are the late appearance of the first symptoms, the lack of effective treatments, the high tendency it has to produce metastasis, and also the problems that its detection presents. Unfortunately, the diagnosis of malignant melanoma continues to be problematic today due to the lack of signals or indicators, called biomarkers, that allow detecting this disease early and accurately, as well as predicting how the disease will progress in a patient once detected.
These previously mentioned characteristics, which make this type of cancer such a serious disease, may be partly attributable to the so-called cancer stem cells (CMCs), a small population of cells that exists in tumors, and that presents the typical characteristics of stem cells. They are responsible for the initiation, growth and maintenance of tumors, as well as for metastases and relapses, even years after a tumor has been eradicated.
That is why this team of scientists led by Juan Antonio Marchal Corrales, professor of the Department of Human Anatomy and Embryology and director of the Drs. Galera y Requena Research on Cancer Stem Cells, belonging to the University of Granada, researcher responsible for the group of advanced therapies of the Biosanitary Research Institute of Granada (ibs.GRANADA) and the MNat: ModelingNature Excellence Unit, has focused on the study of these CMCs, and specifically of small vesicles that act as emissaries of these cells, called exosomes, they produce and send to other cells and tissues as messengers, to communicate through the transfer of certain biomolecules and condition the appearance of metastases.
These exosomes have been shown to be involved in many tumor processes and cells release them and circulate through the blood, representing a very interesting source of biomarkers, since they can be easily isolated from a blood sample. This work focused on the characterization at the molecular level of exosomes produced by CMCs and isolated in blood from patients with malignant melanoma, using metabolomic techniques, a discipline that studies the set of molecules of biological systems, in order to find possible biomarkers for the diagnosis of this disease.
This study is the result of a multidisciplinary work where translational researchers, bioinformatics and clinical researchers belonging to the University of Granada, to the MEDINA Foundation, led by Francisca Vicente and José Pérez del Palacio, director and principal investigator of the screening department respectively, at the Virgen de las Nieves and San Cecilio University Hospitals in Granada, all of them members of the ibs.GRANADA, the University of Vigo, as well as the National Cancer Research Center (CNIO), join forces to take another step in the field of Medicine Personalized or Precision Medicine in Oncology.
In this work, it was first shown that the molecular composition of exosomes produced by CMCs is different from those released by differentiated tumor cells. To do this, from a primary line derived from a patient with malignant melanoma, both types of cells were cultured in large quantities and the exosomes that produce and release into the culture medium were isolated. of the exosomes that they produce, a metabolomic analysis was carried out, which makes it possible to study the set of molecules (metabolites) present in a biological sample. After the extraction and detection of the molecules by means of a sophisticated equipment called mass spectrometer, which allows them to be detected and quantified with high precision, a series of statistical analyzes were carried out to see which molecules were found in the highest concentration in the exosomes of a type of cells and cells. Thus, some lipidic metabolites differentially present in exosomes of CMCs and differentiated tumor cells were tentatively identified.
Metabolomic profile
Subsequently, and following the same scientific approach, a similar study was carried out comparing the metabolomic profile of exosomes isolated from the blood of patients with malignant melanoma in different stages and from healthy individuals who acted as controls. The study concluded that certain metabolites, including some of those previously identified in CMCs, were also present in exosomes isolated from blood in different concentrations between melanoma patients and healthy individuals. By means of the corresponding statistical models, these molecules and their different concentration in the blood would make it possible to distinguish individuals with malignant melanoma from those who do not suffer from it, and therefore are susceptible to potential biomarkers for the diagnosis of this disease.
However, the authors emphasize that this study is only a first approximation, in which the identification of some of these molecules, the complete characterization of those tentatively identified, as well as its repetition with a greater number of samples is still pending. the validation and verification of their clinical application as biomarkers.
Studies like the present one constitute a new avenue for the discovery of cancer biomarkers aimed at improving early diagnosis, prognosis and prediction of response to treatment. And of course these results can be extrapolated to many other tumors, for the search for biomarkers that help us better understand the pathogenesis of these diseases and achieve personalized precision medicine.
The study has been funded by the Ministry of Science, Innovation and Universities (project RTI2018-101309-B-C2 and the José Luis Palacios Ferrer FPU contract with Ref: FPU15/03682), by the Carlos III Health Institute (Project PIE16- 00045), the Ministry of Economy, Knowledge, Business and University of the Junta de Andalucía, the European Regional Development Fund (SOMM17/6109/UGR project, UCE-PP2017-3), the “Cátedra Dres. Galera and Requena for cancer stem cell research” of the UGR and the MEDINA Foundation.
Bibliographic reference:
Palacios-Ferrer JL, García-Ortega MB, Gallardo-Gómez M, García MÁ, Díaz C, Boulaiz H, Valdivia J, Jurado JM, Almazán-Fernández FM, Arias-Santiago S, Amezcua V, Peinado H, Vicente F, Pérez Of the Palace J, Marchal JA. Metabolomic profile of cancer stem cell-derived exosomes from patients with malignant melanoma. Mol Oncol. 2021 Feb 05, 15 (2), 407-428 .. doi: 10.1002 / 1878-0261.12823 .. PMID: 33052601