Marques M P M, Batista de Carvalho A L M, Mamede A P, Dopplapudi A, García Sakai V, Batista de Carvalho L A E
Molecular Physical-Chemistry R&D Unit, Department of Chemistry, University of Coimbra, 3004-535 Coimbra, Portugal.
ISIS Facility, STFC Rutherford Appleton Laboratory, Chilton, Didcot OX11 0QX, United Kingdom.
Struct Dyn. 2020 Sep 8;7(5):054701. doi: 10.1063/4.0000021. eCollection 2020 Sep.
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.
人类细胞从正常状态转变为恶性状态仍然是一个尚未被充分理解的过程。作为揭示恶性肿瘤特定特征和识别癌症特异性标志物的一种创新方法,研究了健康人类细胞与癌细胞之间细胞内水动力学活性的变化。使用准弹性中子散射技术,对雄激素不敏感型前列腺癌、三阴性乳腺癌以及骨肉瘤进行了研究。与健康细胞相比,癌细胞表现出显著更高的可塑性,这在乳腺腺癌中更为明显。此外,数据表明,与三阴性乳腺癌和骨肉瘤相比,前列腺癌细胞表现出最高的可塑性,而骨肉瘤的可塑性明显较低。此外,结果表明正常细胞和癌细胞中不同类型细胞内水分子的灵活性存在差异,以及参与不同运动模式的分子数量也存在差异。从健康细胞转变为癌细胞时,水化水分子的动力学几乎不受影响,而细胞质水(特别是旋转运动)在从正常细胞转变为癌细胞时会发生显著变化。本研究获得的结果可能有助于理解致癌作用和肿瘤转移背后的细胞动力学变化,重点是细胞内水。