Interplay between neural stem cells and glioblastoma: possible role of neurotrophin signaling

Abstract

I have read with great interest the recent article by J. Wang et al., entitled “Neural stem cells promote glioblastoma formation in nude mice” [Clin Transl Oncol (2019) https :// doi.org/10.1007/s1209 4-019-02087 -x] [1]. By co-culturing neural stem cells (NSCs) and glioblastoma (GBM) cells, and co-injecting NSCs and GBM cells in nude mice, the authors provide evidence indicating that NSCs stimulate GBM cell proliferation, migration, and invasion, as well as GBM growth in vivo. NSCs have been proposed as candidate cells of origin in GBM [2]. The study by Wang et al. [1] suggests that the NSC population can also stimulate GBM when present as a component of the tumor niche. This issue has clinical implications, given that NSCs migrate towards GBM tumors [3], and thus their use has been proposed as a therapeutic strategy to deliver anticancer agents to GBMs [4]. Possible mechanisms underlying interactions between NSCs and GBM were not explored in the study by Wang et al. [1]. One could hypothesize that the effects observed in the study are mediated by NSCs secreting growth factors capable of stimulating several aspects of GBM cell function. For example, NSCs express and release the neurotrophin brain-derived neurotrophic factor (BDNF) and lead to an increase in local BDNF levels when transplanted into the mouse brain [5, 6]. The BDNF receptor, tropomyosin receptor kinase B (TrkB), is expressed in GBM as well as in GBM stem cells isolated from fresh human tumors, and BDNF stimulates GBM stem cells [7]. It would be interesting to investigate whether neurotrophin secretion by NSCs is a mechanism mediating their stimulatory actions in GBM. Finally, the findings by Wang et al. [1] suggesting that NSCs promote GBM growth may raise concerns about the use of NSCs as tools in GBM therapy. Therefore, clarifying the biological basis of interactions between NSCs and GBM cells is crucial for future potential clinical developments.