Histamine in the Neural and Cancer Stem Cell Niches
Neural stem cells (NSCs) present in the subventricular zone and in the subgranular zone of the adult brain possess proliferative and self-renewal capacities and are able to generate neurons and glial cells. Under physiologic conditions, these properties are tightly regulated at the neurogenic niche consisting of soluble factors and cell-to-cell interactions that control signaling pathways and genetic expression related to the stemness state. The deregulation of these pathways has been suggested to promote the neoplasic transformation of NSCs into cancer stem cells (CSCs) and the formation of gliomas. In fact, NSCs and CSCs share several characteristics including cell surface receptors and intracellular signalling pathways, several cell markers of immaturity, and affinity for blood vessels. Therefore, understanding the cellular and molecular pathways controlling NSCs properties will shed light on brain cancer development and progression. Among soluble factors able to modulate both NSCs and tumoral cells, histamine is raising attention due to its ability to modulate proliferation, differentiation, and survival of both cell types. This may suggest that the modulation of the histaminergic system could emerge as a novel approach to promote brain repair by neurogenesis stimulation and to hamper the development of brain tumors. In this chapter we discuss recent findings regarding the role of histamine in both neurogenesis and tumorigenesis.
KeywordsStem Cell Glial Fibrillary Acidic Protein Cancer Stem Cell Dentate Gyrus Ependymal Cell
This work was supported by FCT Portugal and FEDER, PTDC/SAU-NEU/104415/2008 and PTDC/SAU-NEU/101783/2008, grant no. 96542, from the Calouste Gulbenkian Foundation and L’Oréal-UNESCO Portugal for Women in Science. Maria Francisca Eiriz acknowledges the MIT-Portugal Program, focus in Bioengineering.
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