Researchers from the ibs.GRANADA show that the mesenchymal stem cells that support the tumor favor the expansion of the most aggressive cancer stem cells
A team of scientists made up of researchers from different national and international institutions, and led by the University of Granada, has shown for the first time that growth factors and proteins (cytokines) released by mesenchymal stem cells (MSC) that surround the tumor It allows selecting and increasing cancer stem cells (CMCs) with chromosomal alterations that make them more aggressive and resistant to treatment.
MSCs are a type of stem cells, present in a wide variety of tissues (bone marrow, blood and umbilical cord tissue, skin, fat or muscle tissue ...) and capable of producing different specialized cells found in body tissues. human. For example, they can differentiate (or specialize) into cartilage cells (chondrocytes), bone cells (osteoblasts), and fat cells (adipocytes).
In-depth knowledge of CMCs is of vital importance to clarify tumor development and evolution, as well as to be able to establish specific diagnostic methods and improve new therapies against these that allow avoiding relapses and metastasis. The conventional culture of CMCs obviates the effect exerted by the tumor microenvironment and all the cells of different origin that make up the tumor, so knowledge of these interactions is crucial.
In this study, a culture medium has been generated from the factors and cytokines released by mesenchymal stem cells that allows obtaining CMCs from samples from patient tumors. Thanks to this medium, it has been possible to select and isolate CMCs from colon cancer and malignant melanoma that possess specific markers of the cell membrane, an increased activity of the enzyme aldehyde dehydrogenase 1, the ability to form spheres when they are cultured in suspension and expressing pumps that allow the elimination of antitumor drugs and, therefore, are more resistant to treatment.
The cells selected with this medium are so tumorigenic that only 10 of these human CMCs are capable of generating tumors in laboratory mice in just 2 weeks, being larger and more aggressive than those generated by CMCs isolated with other culture methodologies. conventional used up to now.
Furthermore, CMCs cultured with this medium present a chromosomal alteration that is characterized by a translocation in the long arm of chromosome number 17 (17q25). Bioinformatic analysis of this area of the chromosome revealed that it is an area where numerous genes are found and encodes for numerous microRNAs that are related to the maintenance of stem cells.
The subsequent analysis of the factors released by mesenchymal stem cells revealed that four cytokines and seven growth factors are directly related to this enrichment capacity of CMCs, and that the combination of only two of them, Interleukin-6 (IL- 6) and hepatocyte growth factor (HGF), is sufficient to obtain an enriched culture in tumor stem cells and to maintain it for longer than the conventional culture medium.
This study not only highlights the role that mesenchymal stem cells play in the maintenance of tumor stem cells, but it has also allowed the generation of a world patent, which includes the United States (WO2016020572A1; US20170226472A1), for a new culture medium that can be applied from basic science for drug screening, for example, to clinical applications that allow the culture of CMCs from patients for their subsequent analysis, or the determination of specific biomarkers of these CMCs, thus allowing to establish a more medicine. personalized and precision cancer.
The study was financed mainly by the Doctors Galera and Requena Chair for Research in Cancer Stem Cells at the UGR and researchers from the universities of Granada and Jaén, belonging to the Unit of Excellence "Modeling Nature: from nano to macro" of the UGR, from the Biobank of the Public Health System of Andalusia (Granada), the Virgen de las Nieves Hospital in Granada, the Houston Methodist Cancer Center, the UM Sylvester Comprehensive Cancer Center of the University of Miami and the Biosanitary Research Institute of Granada (ibs Granada ).