Multiple myeloma: a team from the University of Milan discovered one of the molecular mechanisms involved in extracellular vesicle-mediated communication between bone marrow and cancer
Silencing theoncogene NOTCH with molecules of Anti-sense RNA it is possible to block the pathological communication between tumor and bone marrow which favors the progression of multiple myeloma. The study focused on a particular mode of communication between multiple myeloma And bone marrowand was coordinated by Raffaella ChiaramonteProfessor of General Pathology of theUniversity of Milan (Department of Health Sciences), in collaboration with other Departments of the same university (Medical Biotechnology and Translational Medicine, Clinical and Community Sciences, Oncology and Hemato-Oncology) and with the Hematology Unit of theValduce Hospital of Como and a research group of the‘University of L’Aquila. The results were published in the journal Haematological.
The multiple myeloma it is a haematological neoplasm of plasma cells and its mortality in Italy, in slight decline, is about 4.1 people per 100,000 per year. In general, the development and progression of a tumor is also linked to its ability to modify the behavior of the surrounding cells to make the tumor microenvironment more favorable to the cancer itself. From this point of view, the multiple myeloma it is a type of tumor that more than others needs the support of its own microenvironment. Precisely for this reason, the interaction between myeloma and the microenvironment is extensively studied to identify new therapeutic approaches that block tumor growth.
Multiple myeloma, blocking the NOTCH oncogene with anti-sense RNA molecules can stop the communication between the tumor and the bone marrow
The constant dialogue between myeloma cells and the medullary microenvironment in which they reside can be mediated by direct contact between the various cellular components present in this niche and by the release of soluble factors. Furthermore, according to a recent discovery, such communication can also be fueled by particles of cellular origin surrounded by a double lipid layer, the so-called extracellular vesicles.
These vesicles contain several types of molecular messengers, including proteins, RNA, metabolites, which can thus be transported into nearby and distant cells. The researchers involved in this study discovered one of the molecular mechanisms involved in the communication mediated by the extracellular vesicles released by the multiple myeloma.
Within these vesicles, in particular, theoncogene NOTCH2 which is transferred by them to the cells of the tumor niche, where it alters the biological functions of the microenvironment. In particular, the extracellular vesicles produced by cell lines of multiple myeloma or from cells of bone marrow obtained from biopsies of cancer patients seem to activate two important processes associated with neoplastic progression. The first is thetumor angiogenesis, or the growth of vessels essential to the supply of oxygen and nutrients necessary for tumor growth and metastatic spread. The second process is the stimulation of bone cell differentiationcalled osteoclasts, which by enhancing their osteolytic capacity, or demineralization of bone tissue, cause fractures and severe osteoporosis in over 80% of patients, limiting their quality of life.
In the study, the researchers tried to reproduce some aspects of these processes in the zebrafish, a small fish frequently used in biomedical research. Experiments with zebrafish were carried out in collaboration with Anna PistocchiProfessor of Applied Biology of the Department of Medical Biotechnology and Translational Medicine of the State of Milan. In these animals it has been possible to observe that the extracellular vesicles can carry the signal ofoncogene NOTCH2 also through the blood vessels in distant locations. The data suggest that these vesicles may favor the creation of a favorable medium for new metastatic sites, which would thus be made more accessible by the local formation of new vessels and by the degradation of the bone matrix.
What could be the repercussions of this study? “Silencing the NOTCH2 gene with RNA molecules (shRNA) in myeloma cells, we have verified for the first time that it is possible to block the transfer ofoncogene NOTCH2 through the extracellular vesicles, thus inhibiting their pathological effects. The results obtained open the way to the design of new therapeutic strategies based on RNA drugs, aimed at counteracting the pathological effects of extracellular vesicles in multiple myeloma and in other types of cancer ”, he closes Raffaella Chiaramonte. The research was conducted with the support of AIRC Foundation for Cancer Research.
