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.
Highlights
Cancer is a worldwide health problem, being the second leading cause of death globally (9.6 million deaths in 2018) and expected to rise up to 22 million cases per year within the two decades.[1]
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
Since the mechanical properties and water exchange kinetics of the intracellular milieu were found to be intimately associated with these processes,[11–16] the dynamical profile of water in breast and prostate cancer cells was presently tackled by quasi-elastic neutron scattering (QENS) and compared with their nonneoplastic equivalents, as well as with bone cancer cells.[27]
Summary
Cancer is a worldwide health problem, being the second leading cause of death globally (9.6 million deaths in 2018) and expected to rise up to 22 million cases per year within the two decades.[1]. A successful development of novel anticancer agents relies on a thorough understanding of the carcinogenesis process, i.e., of the specific biochemical and biophysical mechanisms responsible for the normal-to-malignant transformation in cells that may enable both an early diagnosis and the development of selective and improved drugs. Triple-negative breast adenocarcinoma is the most aggressive type of mammary cancer with a prevalence in younger women and with a very poor prognosis, for which little therapeutic progress has been achieved in the past decades.[2,3]. Osteosarcoma, in turn, is the most frequent bone malignancy in children and adolescents and the second most important cause of cancerrelated deaths in this age group, with a limited prognosis regarding metastatic disease (survival < 20%).[5,6]
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