Biological stoichiometry in human cancer

James Elser, Marcia M. Kyle, Marilyn S. Smith, John D. Nagy

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Background. 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. Methodology/Principal Findings. 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, signifkant differences in %P and %RNA between malignant and normal tissues were not seen in liver and kidney and, overall, RNA contributed only - 11 % of total tissue P content. Conclusions/Significance. 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).

Original languageEnglish (US)
Article numbere1028
JournalPLoS One
Volume2
Issue number10
DOIs
StatePublished - Oct 10 2007

Fingerprint

stoichiometry
Stoichiometry
colon
Tumors
Tissue
Colon
Liver
neoplasms
RNA
Lung
lungs
kidneys
Kidney
Neoplasms
liver
Growth
Nucleic Acids
nucleic acids
Ecosystem
Bearings (structural)

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Elser, J., Kyle, M. M., Smith, M. S., & Nagy, J. D. (2007). Biological stoichiometry in human cancer. PLoS One, 2(10), [e1028]. https://doi.org/10.1371/journal.pone.0001028

Biological stoichiometry in human cancer. / Elser, James; Kyle, Marcia M.; Smith, Marilyn S.; Nagy, John D.

In: PLoS One, Vol. 2, No. 10, e1028, 10.10.2007.

Research output: Contribution to journalArticle

Elser, J, Kyle, MM, Smith, MS & Nagy, JD 2007, 'Biological stoichiometry in human cancer', PLoS One, vol. 2, no. 10, e1028. https://doi.org/10.1371/journal.pone.0001028
Elser, James ; Kyle, Marcia M. ; Smith, Marilyn S. ; Nagy, John D. / Biological stoichiometry in human cancer. In: PLoS One. 2007 ; Vol. 2, No. 10.
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