Neural stem cells promote glioblastoma formation in nude mice
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Neural stem cells (NSCs) have been characterized with the ability of self-renewal and neurogenesis, which has inspired lots of studies to clarify the functions of NSCs in neural injury, ischemic stroke, brain inflammation and neurodegenerative diseases. We focused on the relationship of NSCs with glioblastoma, since we have discovered that recurrent glioblastomas were inclined to be derived from subventricular zone (SVZ), where NSCs reside. We want to clarify whether NSCs are involved in glioblastoma relapse.
Immunocytochemistry was used to confirm the stemness of NSCs. The Cell Counting Kit-8 was used to measure the proliferation of cells. Migration abilities were examined by wound healing and transwell assays, and tumor formation abilities were confirmed in nude mice.
We found in experiments that NSCs promoted proliferation of a glioblastoma cell line-Ln229, the migration ability of Ln229 cells was motivated by co-cultured with NSCs. Tumor formation of Ln229 cells was also accelerated in nude mice when co-transplanted with NSCs. In immunohistochemistry, we found that the Sox2- and Ki67-positive cells were much higher in co-transplanted groups than that of control groups.
These results imply the potential role that NSCs play in speeding up tumor formation in the process of glioblastoma relapse, providing the basis for dealing with newly diagnosed glioblastoma patients, which may help postpone the recurrence of glioblastoma as far as possible through preprocessing the tumor-adjacent SVZ tissue.
KeywordsGlioblastoma Neural stem cells Subventricular zone Cancer stem cells
We thank Lixian Wang (Technical Support Center, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Science) for technical assistance in immunocytochemistry.
This work was supported by National Natural Science Foundation of China (Grant no. 81272804, 81301066, 81672824), National Key Technology Research and Development Program (2014BAI04B02) and National High-tech R&D Program of China (863 Program, 2012AA020809).
Compliance with ethical standards
Conflicts of interest
The authors declare that they have no conflicts of interest.
All the studies were approved by the ethic committee of the Chinese People's Liberation Army of China (PLA) General Hospital. All mouse work was performed in accordance with institutional, IACUC and AAALAS guidelines, by the animal protocol 0709-666A. All animal studies were conducted following approval from the Animal Care and Use Committee of Chinese PLA General Hospital.
All the participants have signed the complete informed consent forms for scientific research.
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