Reciprocal effects of conditioned medium on cultured glioma cells and neural stem cells.
Malignant gliomas are among the most intractable brain cancers. Neural stem cells (NSC) are tissue-specific stem cells with self-renewal capacity and the potential to differentiate into glia and neurons. It has been proposed that NSC could serve as a therapeutic vehicle for the treatment of gliomas. Previous studies showed that NSC, after being implanted into the brain, could migrate to the invading tumor border and target infiltrating tumor cells. These findings suggested that NSC and gliomas could interact, although the mechanism is still not well understood. Here we report that the stem-cell state of NSC is disrupted and NSCs become differentiated when they are co-cultured in vitro with a medium in which glioma cells have been cultured (conditioned medium). The ratio of neurons in these differentiated cells is significantly higher than that in the controls (NSC cultured in regular medium). Conditioned medium in which primary NSC have been grown can inhibit proliferation of glioma cells, an effect that was greater with NSC conditioned medium of embryonic mice than neonatal mice. These results suggest that glioma cells and NSC can interact at the niche or micro-environment level, potentially leading to proliferation and differentiation of NSC and suppression of proliferation of glioma cells. These findings may shed new light on the development of novel strategies for the treatment of malignant gliomas.
Chen
Fu Xue
FX
School of Life Sciences, Shanghai University, 99 Shangda Road, Shanghai, 200444, China. chenfuxue@staff.shu.edu.cn
Ren
Wen Wen
WW
Yang
Yang
Y
Shen
Di
D
Zong
Yijia
Y
Xu
Sulei
S
Duan
Yanhong
Y
Qian
Yanrong
Y
Ji
Yonghua
Y
D000818:Animals; D000831:Animals, Newborn; D001973:Bromodeoxyuridine / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D004622:Embryo, Mammalian; D005910:Glioma / Q000737:chemistry*; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D013234:Stem Cells / Q000737:chemistry*; D013778:Tetrazolium Salts; D013844:Thiazoles
D017077:Culture Media, Conditioned; D009419:Nerve Tissue Proteins; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue; D001973:Bromodeoxyuridine