Role of intracellular water in the normal-to-cancer transition in human cells—insights from quasi-elastic neutron scattering

Abstract

The transition from normal to malignant state in human cells is still a poorly understood process. Changes in the dynamical activity of intracellular water between healthy and cancerous human cells were probed as an innovative approach for unveiling particular features of malignancy and identifying specific reporters of cancer. Androgen-unresponsive prostate and triple-negative breast carcinomas were studied as well as osteosarcoma, using the technique of quasi-elastic neutron scattering. The cancerous cells showed a considerably higher plasticity relative to their healthy counterparts, this being more significant for the mammary adenocarcinoma. Also, the data evidence that the prostate cancer cells display the highest plasticity when compared to triple-negative mammary cancer and osteosarcoma, the latter being remarkably less flexible. Furthermore, the results suggest differences between the flexibility of different types of intracellular water molecules in normal and cancerous cells, as well as the number of molecules involved in the different modes of motion. The dynamics of hydration water molecules remain virtually unaffected when going from healthy to cancer cells, while cytoplasmic water (particularly the rotational motions) undergoes significant changes upon normal-to-cancer transition. The results obtained along this study can potentially help to understand the variations in cellular dynamics underlying carcinogenesis and tumor metastasis, with an emphasis on intracellular water.

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

“…These results indicate that water is taken up as a reactant in the net chemical reactions that describe the differential expression of proteins in cancer. Combined with experimental observations of elevated water content in tumors 1–8, this provides the largest body of evidence to date that physicochemical constraints shape protein abundances at the proteome level in living cells. These findings also lend support to the hypothesis of a primary role in cancer for elevated cellular hydration levels 22.…”

“…The generally higher water content of cancer tissue compared to normal tissue was first demonstrated by gravimetric methods 2, 3 and subsequently by NMR, Raman, and terahertz (THz) spectroscopy 4–7. A recent study of different types of cancer cells using quasi‐elastic neutron scattering suggests that they have not only higher water content but also higher plasticity compared to normal cells 8. Additionally, differences in the amounts of “free” or “bound” water, which are detectable using THz spectroscopy, could potentially be used in the classification of benign or malignant tumors 7.…”

Water Dynamics in Cancer Cells: Lessons from Quasielastic Neutron Scattering

“…However, culturing cells in a deuterated environment has been shown to lead to considerable metabolic changes that could manifest as alterations in water dynamics [ 51 ]. Therefore, a less severe approach for deuteration has been used and consists of culturing the cells in non-deuterated media and sequentially washing these with deuterated saline solution [ 52 , 53 , 54 ]. By doing so, only the signal from extracellular water is drastically reduced in the QENS experiment.…”

“…More recently, in 2020, Marques et al used QENS to discuss the role of intracellular water in the normal-to-cancer transition in human cells [ 54 ]. For this, the group performed experiments with cancer cells and their non-tumorigenic counterparts.…”

Uncovering the Dynamics of Confined Water Using Neutron Scattering: Perspectives

“…Incoherent neutron scattering, on the other hand can provide unique and unambiguous access to the self-diffusion coefficient, but the investigations of the diffusion dynamics of living systems using neutron spectrometers has been severely hindered until recently because of the limited flux provided by the instruments. However, the advent of such research has just begun due to the development of the third-generation neutron backscattering instruments [4,30,[46][47][48], but continued growth will depend on the highest-flux and flexibility provided by the backscattering spectrometer MIRACLES. Additionally, neutron scattering offers the unique capability of performing experiments in various extreme environments, such as humidity [49], pressure [50], electrical stimuli [51], pump probe [52].…”