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Reciprocal Signaling between Glioblastoma Stem Cells and Differentiated Tumor Cells Promotes Malignant Progression
| Content Provider | Scilit |
|---|---|
| Author | Wang, Xiuxing Prager, Briana C. Wu, Qiulian Kim, Leo J. Y. Gimple, Ryan C. Shi, Yu Yang, Kailin Morton, Andrew Zhou, Wenchao Zhu, Zhe Obara, Elisabeth Anne Adanma Miller, Tyler E. Song, Anne Lai, Sisi Hubert, Christopher G. Jin, Xun Huang, Zhi Fang, Xiaoguang Dixit, Deobrat Tao, Weiwei Zhai, Kui Chen, Cong Dong, Zhen Zhang, Guoxin Dombrowski, Stephen M. Hamerlik, Petra Mack, Stephen C. Bao, Shideng Rich, Jeremy N. |
| Copyright Year | 2018 |
| Description | Journal: Cell Stem Cell Summary Glioblastoma is the most lethal primary brain tumor; however, the crosstalk between glioblastoma stem cells (GSCs) and their supportive niche is not well understood. Here, we interrogated reciprocal signaling between GSCs and their differentiated glioblastoma cell (DGC) progeny. We found that DGCs accelerated GSC tumor growth. DGCs preferentially expressed brain-derived neurotrophic factor (BDNF), whereas GSCs expressed the BDNF receptor NTRK2. Forced BDNF expression in DGCs augmented GSC tumor growth. To determine molecular mediators of BDNF-NTRK2 paracrine signaling, we leveraged transcriptional and epigenetic profiles of matched GSCs and DGCs, revealing preferential VGF expression by GSCs, which patient-derived tumor models confirmed. VGF serves a dual role in the glioblastoma hierarchy by promoting GSC survival and stemness in vitro and in vivo while also supporting DGC survival and inducing DGC secretion of BDNF. Collectively, these data demonstrate that differentiated glioblastoma cells cooperate with stem-like tumor cells through BDNF-NTRK2-VGF paracrine signaling to promote tumor growth. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5947947/pdf http://www.cell.com/article/S1934590918301176/pdf |
| ISSN | 19345909 |
| e-ISSN | 18759777 |
| DOI | 10.1016/j.stem.2018.03.011 |
| Journal | Cell Stem Cell |
| Issue Number | 4 |
| Volume Number | 22 |
| Language | English |
| Publisher | Elsevier BV |
| Publisher Date | 2018-04-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Cell Stem Cell Cell Tissue Engineering Glioblastoma; Cancer Stem Cell; Neurotrophin; Glioma Stem Cell; Differentiated Glioma Cell; Vgf; Bdnf; Ntrk2 |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Genetics Molecular Medicine |
