Abstract
The combination of thrombosis and the progression of malignant tumors is a well-known fact. However, the reason for this observed pattern remains unclear. The megakaryocyte, a polyploid cell containing up to 64 haploid sets of human chromosomes, detaches platelets in the bone marrow. Megakaryocytes function not only as hematopoietic cells but also as cells involved in innate immunity. Researchers discovered a phenomenon called emperipolesis in the second half of the 20th century. During emperipolesis, cell coexistence is observed: the host cell phagocytoses the guest cell without lysing it, allowing for the mutual exchange of intracellular contents. With this phenomenon, mutual exchange of intracellular contents is possible. Emperipolesis occurs normally in human bone marrow in 4–6% of cases and increases in stress and chronic inflammation. Besides the neutrophils, the “guests” of the megakaryocyte are macrophages and lymphocytes. In addition to emperipolesis, extracellular vesicles transmit tumor information to bone marrow progenitor cells. Next, the information is transmitted to platelets that contribute to the formation of a blood clot, facilitating the adhesion of both exosomes and circulating tumor cells. Targeted delivery of exosomes and lymphocytes to the target tissue is carried out by adhesion molecules — integrins. They determine both intercellular interaction and cooperation between the parenchyma and the stroma. Integrins are the creators of tissue architecture, as they connect components of the intercellular matrix with the cytoskeleton. These molecules are capable of transmitting information bidirectionally — from the cell to the intercellular environment and vice versa — from the environment to the cell.
Thus, during metastasis of malignant tumors, nucleic acids of a tumor nature from neutrophils, macrophages, exosomes, and memory B cells enter the bone marrow. Due to this, the megakaryocyte receives tumor-specific nucleic acids. The megakaryocyte subsequently transmits this information to platelets. We suggest another way that metastasis might start: it could be through the bone marrow, where cells involved in hematopoiesis can stay for years or even decades. These cells may have received nucleic acids that can turn them into cancer cells or start metastases growing.
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