Stem cells and the phenomena of plasticity and diversity: a limiting property of carcinogenesis.
The phenomenon referred to as "stem cell plasticity" brings forth a number of issues and problems related to many biological and medical disciplines. This paper reviews some important questions and opinions concerning both stem cell plasticity and processes associated with stem cells with special emphasis on "tumor stem cells" and their potential role in carcinogenesis. A considerable component of our discussion is devoted to the phenomena associated with stem cell diversity; namely, to the relationship between phenotypic diversity and plasticity. Here we attempt to formulate general definitions of plasticity and diversity and show how these properties are interrelated. To illustrate the problem, we chose a theoretical model relevant to tissue regeneration. The results suggest some theoretical possibilities of tumor development and the reprogramming of tumor cells. It is our opinion that cell plasticity decreases with their stage of differentiation in time. However, plasticity will never be zero, since even highly differentiated cells retain a certain degree of plasticity. Generally speaking, as the number of stem cells decreases, the plasticity of the population decreases--the population has "low plasticity." If we assume that plasticity is a phenomenon applicable to all cells, including tumor cells, the development of a tumor stem cell may result in a profound increase in plasticity. This highly plastic population may participate in processes of tissue regeneration. As we presume existence of a complementary relationship between the plasticity and diversity of stem cells, this highly plastic population may evoke a certain degree of diversity in all cells including tumor cells, and a population of low diversity cells may develop. This condition renders a new degree of diversity in all cells, and a new population of high diversity cells develop. On the grounds of this hypothesis, we predict that in certain circumstances, tumor stem cells may participate in tissue regeneration without initiating tumor development (low diversity cells), or with the imitation of tumor development (high diversity cells). Therefore, it may be presumed that in a certain transition period, tumor stem and progenitor cells may reprogram from the state of diversity (e.g., from low --> high --> low) and stimulate the development of normal tissue. Here the interrelation between the plasticity and diversity of stem cells plays an important role in determining cell fate. Since the two phenomena cannot be temporally separated from each other but are indeed mutually exclusive. We view this situation in a manner similar to the principle of indefiniteness; cells must choose either plasticity or diversity, as both are not possible at the same time.
Filip
Stanislav
S
Department of Oncology and Radiotherapy, Charles University in Prague, Faculty of Medicine and Teaching Hospital, Hradec Králové, Czech Republic. fi lip@fnhk.cz
Mokry
Jaroslav
J
Horacek
Jiri
J
English
Denis
D
D000818:Animals; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D012038:Regeneration