Is there a connection between the nature of stem cell division and the neoplastic process?
As is known, stem cells have the ability to self-renew and cell differentiation, and the strategy aimed at fulfilling these two tasks is implemented in the process of asymmetric division. But in this case, the number of stem cells remains unchanged. However, in the case of disease or damage, the number of stem cells must be increased in order to stop the defects that occur, which implies the presence of dynamic control over their number.
In all organisms, the increase in the number of cells is due to symmetrical mitotic division. In the case of stem cells, they can also divide symmetrically, supporting both self-renewal and differentiation. Evidence of the presence of symmetrical cell division was obtained both on model objects – nematode roundworms and fruit fly drosophila, and on vertebrates (including mammals).
The possibility of symmetrical self-renewal of stem cells is of great importance for ontogenesis, providing plasticity of development, problems of growth of the organism and increased ability to regenerate. However, at the same time, it also carries the risk of developing cancer.
Thus, studies on drosophila have shown that in case of violation of the mechanism of asymmetric division of neuroblasts, they begin to divide symmetrically and form tumors. The evolutionary process has consolidated the conservative connection between the ability to asymmetric division and the suppression of carcinogenesis. For example, in drosophila, the APC (adenomatous polyposis coli) gene is necessary for the asymmetric division of spermatogonial stem cells and acts as a tumor suppressor in the intestinal epithelium of mammals. Deletion of other homologous genes (LGL, HUGL-1) is often detected in the study of human tumor cells, and in mice leads to a loss of polarity and dysplasia of the central nervous system.
Other facts confirming the link between symmetrical cell division and cancer are related to the observation that some gene products can induce symmetrical division and function as oncogenes in mammalian cells. For example, this applies to the atypical protein kinase aPKC, which in drosophila functions with symmetrical division of neuroblasts and has been identified as an oncogene in human lung cancer.
The different fate of cells in asymmetric division is associated with the location of the division spindle and the functioning of the centrosomes.
So, the long-term symmetrical division of mammalian stem cells during embryonic development creates a pool of stem cells and tissues capable of regeneration. It is possible that the ability to switch between symmetrical and asymmetric division is the main adaptive mechanism that ensures regeneration and longevity. But the potential price for the frequent use of symmetrical stem cell division is an increase in the frequency of cancer that occurs during the transformation of somatic stem cells.
The idea that symmetrical division is associated with neoplastic proliferation remains at the hypothesis level for the time being. However, it is possible that the study of the asymmetric division machine will allow identifying new important mechanisms suppressing oncogenesis. And the main question for future research is how the stem cell switches between asymmetric and symmetrical division. Elucidation of the molecular nature of the regulation of this switch is important not only for the fundamental biology of stem cells, but also has great clinical significance for the therapeutic use of stem cells.
Source: Nature, Vol. 44, No. 29, 2006.