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Tumor acidity as evolutionary spite.

Alfarouk KO, Muddathir AK, Shayoub ME - Cancers (Basel) (2011)

Bottom Line: Most cancer cells shift their metabolic pathway from a metabolism reflecting the Pasteur-effect into one reflecting the Warburg-effect.Thus, diminishing the selective environment most probably interferes with the spite process.Such interference has been recently utilized in cancer treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of Biotechnology, Africa City of Technology, Khartoum, Sudan. Alfarouk@hala-alfarouk.org.

ABSTRACT
Most cancer cells shift their metabolic pathway from a metabolism reflecting the Pasteur-effect into one reflecting the Warburg-effect. This shift creates an acidic microenvironment around the tumor and becomes the driving force for a positive carcinogenesis feedback loop. As a consequence of tumor acidity, the tumor microenvironment encourages a selection of certain cell phenotypes that are able to survive in this caustic environment to the detriment of other cell types. This selection can be described by a process which can be modeled upon spite: the tumor cells reduce their own fitness by making an acidic environment, but this reduces the fitness of their competitors to an even greater extent. Moreover, the environment is an important dimension that further drives this spite process. Thus, diminishing the selective environment most probably interferes with the spite process. Such interference has been recently utilized in cancer treatment.

No MeSH data available.


Related in: MedlinePlus

Here we propose a hypothetical model in which the environment where the player interactions are carried out (i.e., the acidic extracellular space; blue background) can play an important role in determining the choice and dynamics of spite. At this point, it is not possible to determine if there is a space-time quadrant where the environment has a greater or lesser effect and this will be an interesting point for future research. (a) Because microenvironment acidity-induced cancer spite (MAICS) blunts the immune system [33], interference with MAICS would probably create a shifting to Wilsonian spite. Thus, the third party reappears (Z-axis in (b) (Wilsonian spite) (b) This kind of shifting does not misconstrue to malignant and normal cells only but a spite process could happen also between secondary tumor cells (cannibal cells) and primary tumor cells.
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f2-cancers-03-00408: Here we propose a hypothetical model in which the environment where the player interactions are carried out (i.e., the acidic extracellular space; blue background) can play an important role in determining the choice and dynamics of spite. At this point, it is not possible to determine if there is a space-time quadrant where the environment has a greater or lesser effect and this will be an interesting point for future research. (a) Because microenvironment acidity-induced cancer spite (MAICS) blunts the immune system [33], interference with MAICS would probably create a shifting to Wilsonian spite. Thus, the third party reappears (Z-axis in (b) (Wilsonian spite) (b) This kind of shifting does not misconstrue to malignant and normal cells only but a spite process could happen also between secondary tumor cells (cannibal cells) and primary tumor cells.

Mentions: Here, we propose that aerobic glycolysis confers an evolutionary advantage due to an adaptive strategy that is commonly termed “spite”. In brief, an organism can evolve a less fit phenotype only if it alters the local adaptive landscape in such a way that it reduces the fitness of all competing populations even more. So, cancer cells, as actors, increase their fitness compared to normal cells as recipients. The acidic environment will select for acid-adapted phenotypes not the glycolytic phenotype. Only after this adaptation will the glycolytic phenotype confer an advantage. This combination of phenotypes then confers an advantage because it increases extracellular matrix (ECM) degradation to facilitate invasion, induces death in normal cells, increases vascular endothelial growth factor (VEGF) release, and reduces the effectiveness of cytotoxic T cells in generating an immune response to tumor antigens. In this general theory, there has developed two types of spites: (i) Hamiltonian spite and (ii) Wilsonian spite, which is a modified Hamiltonian spite because he added a third party that gains benefit or costs the interaction of actor and recipient [4] that could be represented by the immune system in our model (z-axis) (see Figure 1). Here, we propose the environment as an additional fourth dimension because spite might not occur in the absence of a suitable environment (see Figure 2a).


Tumor acidity as evolutionary spite.

Alfarouk KO, Muddathir AK, Shayoub ME - Cancers (Basel) (2011)

Here we propose a hypothetical model in which the environment where the player interactions are carried out (i.e., the acidic extracellular space; blue background) can play an important role in determining the choice and dynamics of spite. At this point, it is not possible to determine if there is a space-time quadrant where the environment has a greater or lesser effect and this will be an interesting point for future research. (a) Because microenvironment acidity-induced cancer spite (MAICS) blunts the immune system [33], interference with MAICS would probably create a shifting to Wilsonian spite. Thus, the third party reappears (Z-axis in (b) (Wilsonian spite) (b) This kind of shifting does not misconstrue to malignant and normal cells only but a spite process could happen also between secondary tumor cells (cannibal cells) and primary tumor cells.
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Related In: Results  -  Collection

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f2-cancers-03-00408: Here we propose a hypothetical model in which the environment where the player interactions are carried out (i.e., the acidic extracellular space; blue background) can play an important role in determining the choice and dynamics of spite. At this point, it is not possible to determine if there is a space-time quadrant where the environment has a greater or lesser effect and this will be an interesting point for future research. (a) Because microenvironment acidity-induced cancer spite (MAICS) blunts the immune system [33], interference with MAICS would probably create a shifting to Wilsonian spite. Thus, the third party reappears (Z-axis in (b) (Wilsonian spite) (b) This kind of shifting does not misconstrue to malignant and normal cells only but a spite process could happen also between secondary tumor cells (cannibal cells) and primary tumor cells.
Mentions: Here, we propose that aerobic glycolysis confers an evolutionary advantage due to an adaptive strategy that is commonly termed “spite”. In brief, an organism can evolve a less fit phenotype only if it alters the local adaptive landscape in such a way that it reduces the fitness of all competing populations even more. So, cancer cells, as actors, increase their fitness compared to normal cells as recipients. The acidic environment will select for acid-adapted phenotypes not the glycolytic phenotype. Only after this adaptation will the glycolytic phenotype confer an advantage. This combination of phenotypes then confers an advantage because it increases extracellular matrix (ECM) degradation to facilitate invasion, induces death in normal cells, increases vascular endothelial growth factor (VEGF) release, and reduces the effectiveness of cytotoxic T cells in generating an immune response to tumor antigens. In this general theory, there has developed two types of spites: (i) Hamiltonian spite and (ii) Wilsonian spite, which is a modified Hamiltonian spite because he added a third party that gains benefit or costs the interaction of actor and recipient [4] that could be represented by the immune system in our model (z-axis) (see Figure 1). Here, we propose the environment as an additional fourth dimension because spite might not occur in the absence of a suitable environment (see Figure 2a).

Bottom Line: Most cancer cells shift their metabolic pathway from a metabolism reflecting the Pasteur-effect into one reflecting the Warburg-effect.Thus, diminishing the selective environment most probably interferes with the spite process.Such interference has been recently utilized in cancer treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of Biotechnology, Africa City of Technology, Khartoum, Sudan. Alfarouk@hala-alfarouk.org.

ABSTRACT
Most cancer cells shift their metabolic pathway from a metabolism reflecting the Pasteur-effect into one reflecting the Warburg-effect. This shift creates an acidic microenvironment around the tumor and becomes the driving force for a positive carcinogenesis feedback loop. As a consequence of tumor acidity, the tumor microenvironment encourages a selection of certain cell phenotypes that are able to survive in this caustic environment to the detriment of other cell types. This selection can be described by a process which can be modeled upon spite: the tumor cells reduce their own fitness by making an acidic environment, but this reduces the fitness of their competitors to an even greater extent. Moreover, the environment is an important dimension that further drives this spite process. Thus, diminishing the selective environment most probably interferes with the spite process. Such interference has been recently utilized in cancer treatment.

No MeSH data available.


Related in: MedlinePlus