Biological stoichiometry in human cancer

• Published in: PloS one Vol. 2; no. 10; p. e1028
• Main Authors: Elser, James J, Kyle, Marcia M, Smith, Marilyn S, Nagy, John D
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10.10.2007; Public Library of Science (PLoS)
• Subjects: Apoptosis; Biogeography; Biology; Biomass; Biopsy; Biota; Cancer; Cell division; Cell growth; Chemical elements; Colon; Colon cancer; Colonic Neoplasms - pathology; Colorectal cancer; Deoxyribonucleic acid; Disease prevention; DNA; DNA - chemistry; Ecology; Ecology - methods; Ecosystems; Evolutionary Biology; Gastrointestinal diseases; Gene Expression Regulation, Neoplastic; Genes; Growth rate; Homeostasis; Humans; Hypotheses; Kidneys; Life sciences; Ligands; Liver; Liver cancer; Lung cancer; Lung Neoplasms - pathology; Lungs; Metabolism; Models, Biological; Models, Theoretical; Mortality; Mutation; Neoplasms - pathology; Nitrogen; Nitrogen - analysis; Nucleic acids; Oncology; Organs; Phosphorus; Phosphorus - analysis; Phosphorus content; Protein biosynthesis; Protein synthesis; Ribonucleic acid; Ribosomal RNA; RNA; RNA - chemistry; RNA, Ribosomal - chemistry; rRNA; Tissue Distribution; Tissues; Tumors; United States > US; Kansas City Missouri; Arizona
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0001028

A growing tumor in the body can be considered a complex ecological and evolutionary system. A new eco-evolutionary hypothesis (the "Growth Rate Hypothesis", GRH) proposes that tumors have elevated phosphorus (P) demands due to increased allocation to P-rich nucleic acids, especially ribosomal RNA, to meet the protein synthesis demands of accelerated proliferation. We determined the elemental (C, N, P) and nucleic acid contents of paired malignant and normal tissues from colon, lung, liver, or kidney for 121 patients. Consistent with the GRH, lung and colon tumors were significantly higher (by approximately two-fold) in P content (fraction of dry weight) and RNA content and lower in nitrogen (N):P ratio than paired normal tissue, and P in RNA contributed a significantly larger fraction of total biomass P in malignant relative to normal tissues. Furthermore, patient-specific differences for %P between malignant and normal tissues were positively correlated with such differences for %RNA, both for the overall data and within three of the four organ sites. However, significant differences in %P and %RNA between malignant and normal tissues were not seen in liver and kidney and, overall, RNA contributed only approximately 11% of total tissue P content. Data for lung and colon tumors provide support for the GRH in human cancer. The two-fold amplification of P content in colon and lung tumors may set the stage for potential P-limitation of their proliferation, as such differences often do for rapidly growing biota in ecosystems. However, data for kidney and liver do not support the GRH. To account for these conflicting observations, we suggest that local environments in some organs select for neoplastic cells bearing mutations increasing cell division rate ("r-selected," as in colon and lung) while conditions elsewhere may select for reduced mortality rate ("K-selected," as in liver and kidney).