Details

Autor(en) / Beteiligte

• Wang, Xiuxing
• Prager, Briana C.
• Wu, Qiulian
• Kim, Leo J.Y.
• Gimple, Ryan C.
• Shi, Yu
• Yang, Kailin
• Morton, Andrew R.
• 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.

Titel

Reciprocal Signaling between Glioblastoma Stem Cells and Differentiated Tumor Cells Promotes Malignant Progression

Ist Teil von

• Cell stem cell, 2018-04, Vol.22 (4), p.514-528.e5

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2018

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •Differentiated tumor cells cooperate with glioma stem cells to promote tumor growth•Differentiated glioma cells secrete BDNF to stimulate NTRK2 on glioma stem cells•The neurotrophin BDNF induces glioma stem cells to secrete the VGF neuropeptide•VGF promotes survival and growth of both stem-like and differentiated tumor cells Wang et al. investigate reciprocal signaling between glioma stem cells and their differentiated glioblastoma cell progeny. The authors demonstrate that differentiated tumor cells promote the glioblastoma hierarchy and tumor growth through a paracrine feedback loop of neurotrophin signaling in cooperation with stem cell-like tumor cells.