Abstract
Tumors can be viewed as evolving ecological systems, in which heterogeneous populations of cancer cells compete with each other and somatic cells for space and nutrients within the ecosystem of the human body. According to the growth rate hypothesis (GRH), increased phosphorus availability in an ecosystem, such as the tumor micro-environment, may promote selection within the tumor for a more proliferative and thus potentially more malignant phenotype. The applicability of the GRH to tumor growth is evaluated using a mathematical model, which suggests that limiting phosphorus availability might promote intercellular competition within a tumor, and thereby delay disease progression. It is also shown that a tumor can respond differently to changes in its micro-environment depending on the initial distribution of clones within the tumor, regardless of its initial size. This suggests that composition of the tumor as a whole needs to be evaluated in order to maximize the efficacy of therapy.
Highlights
Cancer can be viewed as an ecological system: a tumor is a heterogeneous population of cells, including both malignant and non-transformed somatic cells of the stroma, which compete for space and nutrients within the dynamic environment of the human body [1,2,3,4]
This process involves generating NADPH, which is used for fatty acid synthesis, and ribose-5phosphate, which is used for synthesis of nucleotides and nucleic acids [5]
These considerations underlie the growth rate hypothesis (GRH), which suggests that highly proliferative cells are characterized by relatively low C:P stoichiometry due to their upregulation of the P-rich ribosomes needed to support reproduction [6,7,8]
Summary
Cancer can be viewed as an ecological system: a tumor is a heterogeneous population of cells, including both malignant and non-transformed somatic cells of the stroma, which compete for space and nutrients within the dynamic environment of the human body [1,2,3,4]. Glycolytic intermediates obtained from the breakdown of glucose are used for the biosynthesis of nucleic acids via the pentose phosphate pathway This process involves generating NADPH, which is used for fatty acid synthesis, and ribose-5phosphate, which is used for synthesis of nucleotides and nucleic acids [5]. These considerations underlie the growth rate hypothesis (GRH), which suggests that highly proliferative cells are characterized by relatively low C:P stoichiometry due to their upregulation of the P-rich ribosomes needed to support reproduction [6,7,8]. The second prediction has been experimentally verified [9,10]; the first prediction appears to be supported in cancers of the colon and the lung but not in the kidney or liver, suggesting the possibility that the micro-environment in these two organs may favor selection of clones with propensity for apoptosis evasion rather than increased proliferative potential [11]
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