Center for Drug Research & Development and Pharmacokinetic Applications (ARGEFAR), Ege University, 35100, Izmir, Turkey.
Department of Stem Cell, Ege University Health Science Institute, Izmir, 35100, Turkey.
Analyst. 2019 Mar 21;144(6):2138-2149. doi: 10.1039/c9an00093c. Epub 2019 Feb 11.
Current cancer treatments destroy the tumor mass but cannot prevent the recurrence of cancer. The heterogeneous structure of the tumor mass includes cancer stem cells that are responsible for tumor relapse, treatment resistance, invasion and metastasis. The biology of these cells is still not fully understood; therefore, effective treatments cannot be developed sufficiently. Herein, attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy, combined with unsupervised multivariate analysis, was applied to prostate cancer stem cells (CSCs), non-stem cancer cells (non-CSCs) and normal prostate epithelial cells to elucidate the molecular mechanisms and features of CSCs, which are crucial to improving the target specific therapies. This work revealed the spectral differences in the cellular mechanisms and biochemical structures among three different cell types. Particularly, prostate CSCs exhibit differences in the lipid composition and dynamics when compared to other cell types. CSCs also harbor pronounced differences in their major cellular macromolecules, including differences in the protein amount and content (mainly α-helices), the abundance of nucleic acids (DNA/RNA), altered nucleic acid conformation and carbohydrate composition. Interestingly, macromolecules containing the C[double bond, length as m-dash]O groups and negatively charged molecules having the COO groups are abundant in prostate CSCs in comparison to prostate non-CSCs and normal prostate cells. Overall, this study demonstrates the potential use of ATR-FTIR spectroscopy as a powerful tool to obtain new insights into the understanding of the CSC features, which may provide new strategies for cancer treatment by selectively targeting the CSCs.
目前的癌症治疗方法虽然可以破坏肿瘤团块，但却无法预防癌症的复发。肿瘤团块的异质性结构包括肿瘤干细胞，这些细胞是导致肿瘤复发、治疗耐药、侵袭和转移的罪魁祸首。这些细胞的生物学特性尚未完全阐明，因此无法开发出有效的治疗方法。在这里，我们应用衰减全反射-傅里叶变换红外（ATR-FTIR）光谱结合无监督多元分析方法，研究前列腺癌干细胞（CSC）、非干细胞癌（non-CSC）和正常前列腺上皮细胞，以阐明 CSC 的分子机制和特征，这对于提高靶向特异性治疗至关重要。这项工作揭示了三种不同细胞类型之间细胞机制和生化结构的光谱差异。特别是，与其他细胞类型相比，前列腺 CSC 的脂质组成和动力学存在差异。CSC 还在其主要细胞大分子方面存在明显差异，包括蛋白质含量和含量（主要为α-螺旋）、核酸（DNA/RNA）丰度、核酸构象改变和碳水化合物组成的差异。有趣的是，与前列腺 non-CSC 和正常前列腺细胞相比，CSC 中含有大量 C[双键，长度为 m-dash]O 基团和带负电荷的分子（含 COO 基团）的大分子丰富。总的来说，本研究表明 ATR-FTIR 光谱作为一种强大的工具，具有深入了解 CSC 特征的潜力，这可能为通过选择性靶向 CSC 提供新的癌症治疗策略。
