Migration of cancer cells
Scientists have described the earliest stages of tumor metastasis
Most cells of a living organism are interconnected by intercellular contacts. To break them, the cell has to substantially rebuild the entire internal frame. Russian scientists have found out exactly how its reorganization occurs and what role it plays in the appearance of metastases — secondary tumor foci. It turns out that a well—known participant in the development of cancer — the epidermal growth factor - so changes the protein that binds the strong connecting threads of the cell frame that it can no longer hold the frame and the contacts between the cells disintegrate.
The scheme of the transition of cells into a migratory form under the action of the growth factor EGF.
Interestingly, there is a lack of this protein in cancer cells, and therefore the restoration of the normal level of its synthesis in the cell with the help of gene therapy can serve as one of the ways to combat metastases. The results of the study are presented in the journal Cells (Zhitnyak et al., Early Events in Actin Cytoskeleton Dynamics and E-Cadherin-Mediated Cell-Cell Adhesion during Epithelial-Mesenchymal Transition). The project is supported by a grant from the Russian Science Foundation.
Activation of cell migration under the action of growth factor EGF. Source: Natalia Glushankova.
The researchers found that under the influence of EGF, the actin-binding protein EPLIN changes, after which the actin cytoskeleton loses rigidity and contacts between cells disintegrate. Interestingly, there is a lack of EPLIN protein in cancer cells, and therefore restoring the normal level of its synthesis in the cell with the help of gene therapy can serve as one of the ways to combat metastases.
According to the World Health Organization, cancer is the second leading cause of death in the world. In 2018, this disease claimed the lives of 9.6 million people. Its treatment is primarily complicated by the fact that cancer cells are able to move around the body, creating new tumor foci — metastases. In order to be able to move, the cage must break contacts with its surrounding neighbors and become flexible and maneuverable from a rigid fixed structure. To do this, it is necessary to disassemble the frame and use its elements for movement — pull out the "beams" from the walls and make "paddles" out of them. In the cell, of course, the frame is not wooden, but made of thin but strong strands of actin protein, and it is called a cytoskeleton. Such a restructuring is not unique to cancer cells. For example, in the skin, such activation occurs during the healing of wounds.
Until recently, it remained unclear how immobile, tightly coupled cells turn into migrating ones. Scientists from the N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russia were able to describe the interrelated changes in the structures of the actin cytoskeleton and intercellular contacts that allow cells to break ties with each other and acquire the ability to migrate. To do this, the researchers observed under a microscope the behavior of cells in response to the effects of epidermal growth factor involved in wound healing and tumor metastasis. This was made possible by the glow of proteins that provide contacts between cells. Scientists have achieved this effect by introducing a special genetic construct that adds a luminous part to the studied molecules.
Destruction and restructuring of intercellular contacts. Source: Svetlana Rubtsova.
The researchers found that exposure to growth factor leads to a change in the actin-binding protein EPLIN, after which it cannot hold the actin cytoskeleton in a rigid position, and contacts between cells disintegrate. Interestingly, there is a lack of EPLIN protein in cancer cells, and therefore the restoration of the normal level of its synthesis in the cell with the help of gene therapy can serve as one of the ways to combat metastases.
"Recently, it has been shown that the most important role in the progression of oncological diseases is played by tumor stem cells, which have a high ability to metastasize. In addition, they are extremely resistant to chemotherapy and can block the body's immune response. The study of the mechanisms regulating the processes of migration of tumor cells is of great importance for understanding the pathogenesis of oncological diseases, which is certainly important for the development of new effective methods of their targeted therapy," said project manager Natalia Glushankova, Doctor of Biological Sciences, Head of the Laboratory of Mechanisms of Carcinogenesis of the N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Health Russia.
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