Tumangelova-Yuzeir Kalina, Minkin Krassimir, Angelov Ivan, Ivanova-Todorova Ekaterina, Kurteva Ekaterina, Vasilev Georgi, Arabadjiev Jeliazko, Karazapryanov Petar, Gabrovski Kaloyan, Zaharieva Lidia, Genova Tsanislava, Kyurkchiev Dobroslav
Laboratory of Clinical Immunology, University Hospital "St. Ivan Rilski", Medical University of Sofia, 1431 Sofia, Bulgaria.
Clinic of Neurosurgery, University Hospital "St. Ivan Rilski", Medical University of Sofia, 1431 Sofia, Bulgaria.
Curr Issues Mol Biol. 2023 Mar 21;45(3):2580-2596. doi: 10.3390/cimb45030169.
The central hypothesis for the development of glioblastoma multiforme (GBM) postulates that the tumor begins its development by transforming neural stem cells into cancer stem cells (CSC). Recently, it has become clear that another kind of stem cell, the mesenchymal stem cell (MSC), plays a role in the tumor stroma. Mesenchymal stem cells, along with their typical markers, can express neural markers and are capable of neural transdifferentiation. From this perspective, it is hypothesized that MSCs can give rise to CSC. In addition, MSCs suppress the immune cells through direct contact and secretory factors. Photodynamic therapy aims to selectively accumulate a photosensitizer in neoplastic cells, forming reactive oxygen species (ROS) upon irradiation, initiating death pathways. In our experiments, MSCs from 15 glioblastomas (GB-MSC) were isolated and cultured. The cells were treated with 5-ALA and irradiated. Flow cytometry and ELISA were used to detect the marker expression and soluble-factor secretion. The MSCs' neural markers, Nestin, Sox2, and glial fibrillary acid protein (GFAP), were down-regulated, but the expression levels of the mesenchymal markers CD73, CD90, and CD105 were retained. The GB-MSCs also reduced their expression of PD-L1 and increased their secretion of PGE2. Our results give us grounds to speculate that the photodynamic impact on GB-MSCs reduces their capacity for neural transdifferentiation.
多形性胶质母细胞瘤（GBM）发生发展的核心假说是，肿瘤通过将神经干细胞转化为癌症干细胞（CSC）来开始其发展过程。最近，另一种干细胞，即间充质干细胞（MSC），在肿瘤基质中的作用已变得清晰。间充质干细胞除了具有其典型标志物外，还能表达神经标志物并具备神经转分化能力。从这个角度推测，间充质干细胞可能产生癌症干细胞。此外，间充质干细胞通过直接接触和分泌因子来抑制免疫细胞。光动力疗法旨在使光敏剂在肿瘤细胞中选择性积聚，在照射后形成活性氧（ROS），引发细胞死亡途径。在我们的实验中，分离并培养了来自15例胶质母细胞瘤的间充质干细胞（GB - MSC）。对这些细胞用5 - 氨基乙酰丙酸（5 - ALA）处理并进行照射。采用流式细胞术和酶联免疫吸附测定（ELISA）检测标志物表达和可溶性因子分泌情况。间充质干细胞的神经标志物巢蛋白（Nestin）、性别决定区Y框蛋白2（Sox2）和胶质纤维酸性蛋白（GFAP）表达下调，但间充质标志物CD73、CD90和CD105的表达水平得以保留。GB - MSC还降低了程序性死亡配体1（PD - L1）的表达，并增加了前列腺素E2（PGE2）的分泌。我们的结果使我们有理由推测，光动力对GB - MSC的影响降低了它们的神经转分化能力。
