March 2, 2007

Cells That Did Not Find Place In Life

The majority of cells of a multicellular organism have in literal sence to seek their place, and far from all of them succeed in doing that. The cell being in permanent futile search is a cancer cell. This hypothesis was set forward by Russian scientists Yuri Vasiliev and I.M. Gelfand in the review article published in the Biochemistry journal (2006, Volume 71, No. 8).

For an organism to originate from cells, it is necessary that cells could find each other. To this end, they undertake searching migrations. As a rule, searching migration has two stages. At the search stage, a group of cells or even not cells per se but their processes move in a random way along acellular spaces of the organism, one might say, they fumble about by touch. Some of them grope after something, and then there comes a stage of choice for them. Migrating cells that have achieved definite places in the organism, stop and start differentiation. Embyronic growth is impossible without searching migration. In particular, when the nervous system is being formed, nerve cells of the spinal cord rudiment release processes (axons) into the body cavity, the processes touch the cavity and within some time they hit on some "target", for example, muscle rudiments. Then synapse - neuromuscular junction - occurs. Axons from other sections of the brain find rudiments of other organs. Vessel growth can also be considered as peculiar searching reactions, where ends of ramifying capillaries are at first looked for, and then the territory is selected for blood supply. Wound healing begins with searching migration. The choice is as follows: a cell may find its place and make part of an organ or a tissue, or it may not. Unsuccessful search is a commonplace. Thus, when neuromuscular contacts are being formed, only the minority of axons manage to grope the "target". All other axons and the cells they belong to turn out to be redundant and are subject to extermination - apoptosis.

Malignancy of cancer cells, that is their ability to leave the normal tissue and to spread across the body, is akin to searching migration. However, such migration is considered by the researchers as a pathologic one. Pathologic migration differs radically from the normal one by the fact that it possesses only the first part - wandering- but the choice is absent. Apparently, this pathology occurred as a result of genetic abnormalities in the normal search mechanisms. Malignant cells are constantly wandering in the surrounding tissue, but they do not stop and do not start differentiation. Within the tumors per se, cell displacements are spontaneous and confused. At face value, the cells that did not find their place are subject to destruction, but cancer cells are deprived of the ability for apoptosis, therefore, they survive and reproduce. If the carcinogenesis process has already gone far, cancer cells can leave their native tumor, "wander" rather far from it and form metastases. At earlier stages of carcinogenesis, the cells still preserve some ability for choice, but they pass on to it under the influence of some other factors. Even in the non-malignant tumors, some part of cells is always in the state of search: it reproduces and migrates.

The researchers emphasize that a cancer cell can be called an eternal finder only as a very rough approximation, and all details of the hypothesis suggested by them require experimental validation.


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