Water as a reactant in the differential expression of proteins in cancer

Abstract

Introduction. How proteomes differ between normal tissue and tumor microenvironments is an important question for cancer biochemistry. Methods. More than 250 datasets for differentially expressed (up‐ and downregulated) proteins compiled from the literature were analyzed to calculate the stoichiometric hydration state, which represents the number of water molecules in theoretical mass‐balance reactions to form the proteins from a set of basis species. Results. The analysis shows increased stoichiometric hydration state of differentially expressed proteins in cancer compared to normal tissue. In contrast, experiments with different cell types grown in 3D compared to monolayer culture, or exposed to hyperosmotic conditions under high salt or high glucose, cause proteomes to “dry out” as measured by decreased stoichiometric hydration state of the differentially expressed proteins. Conclusion. These findings reveal a basic physicochemical link between proteome composition and water content, which is elevated in many tumors and proliferating cells.

A thermodynamic model for water activity and redox potential in evolution and development

“…The compositional analysis uncovers decreasing stoichiometric hydration state of proteins in monolayers [26]. Taken together, these findings support the hypothesis that water loss, as measured by the stoichiometric hydration state of proteomes, is a feature of cell-cell interactions, and possibly more rigid cellular or multicellular structures.…”

“…All figures were created in R [62] using the contributed packages canprot version 1.1.0 [26] (available on the Comprehensive R Archive Network (CRAN)) and CHNOSZ [48] (development version > 1.4.0, which is available at https://r-forge.r-project.org/projects/chnosz/). Specifically, functions in the canprot package were used for calculating compositional metrics from amino acid compositions of proteins, and CHNOSZ was used for the thermodynamic calculations.…”

“…So that n H 2 O and Z C can be viewed as independent variables, it is important to choose basis species where their covariation is reduced. Accordingly, the basis species glutamine, glutamic acid, cysteine, H 2 O, and O 2 (denoted "QEC") were chosen for this analysis [26,44]. Z C forms a strikingly smooth hump between PS 1 and 11 then increases rapidly to the maximum at PS 14, followed by a smaller decline to PS 16, which corresponds to Homo sapiens.…”

“…Conversely, relatively high water content has been recognized for over a century as a biochemical characteristic of cancer tissue [18][19][20][21][22], and some authors have highlighted parallel trends of higher water content in both cancer and embryonic tissue [23][24][25]. Models are available to predict water activity from the water content of foods [8], but there is a pressing need to relate observations of water content in normal and pathological states to water activity ( [26]; see also [24, p. 189]), which is a better thermodynamic measure of the potential for hydration in biochemical reactions.…”

“…By applying a compositional analysis to proteomic data, it can be shown that water is consumed as a reactant in the differential expression of proteins of many cancer types compared to normal tissues [26]. This observation suggests that increasing water activity may be a driver for the observed biochemical changes at the proteome level, but a thermodynamic model should be developed to quantify this prediction.…”