Para- and Autocrine Mediators in the Glioma Microenvironment
Unregulated growth, apoptosis-resistance, invasion, strongly increased angiogenesis, and immunosuppression are hallmarks of gliomas. Drivers of these tumor-promoting processes are several auto- and paracrine factors, mostly bioactive peptides. Among them,
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Para- and Autocrine Mediators in the Glioma Microenvironment Kirsten Hattermann and Rolf Mentlein
Abstract
Unregulated growth, apoptosis-resistance, invasion, strongly increased angiogenesis, and immunosuppression are hallmarks of gliomas. Drivers of these tumor-promoting processes are several auto- and paracrine factors, mostly bioactive peptides. Among them, distinct neuropeptides, chemokines, growth factors, and cytokines play a prominent role. Since receptors for neuropeptides are often overexpressed on glioma cells, derivatives are increasingly used for imaging/diagnosis and radiotherapy, whereas clinical significance of agonists or antagonists remains questionable. Chemokines and their receptors significantly contribute to tumor growth and progression by exerting not only chemotactic but also proliferative and anti-apoptotic effects. Next to these small peptides, a multitude of classical growth factors and their receptors with tyrosine kinase activity are driving players of glioma cell progression. Growth factor receptors on glioma cells are partly overexpressed or constitutively activated through mutations, and therefore appear prominent targets for anti-glioma therapies. Several cytokines are heavily produced by glioma cells and exhibit not only immune-modulatory functions, but favor glioma cell proliferation, maintenance for the stem cell character of glioma stem(-like) cells, and may attract stroma cells. Apart from peptides/proteins, some lipid and also nutrient factors are additional drivers of glioma progression. Thus, factors produced by glioma cells (or glioma stem-like cells) exert autocrine as well as paracrine actions on endothelial (angiogenesis factors), microglial, and other cells. Vice versa, bloodborne factors or those produced by the glioma microenvironment drive tumor progression in complex ways. Despite its complexity, this network of auto- and paracrine mediators provides excellent targets for glioma diagnosis, imaging, and therapies.
K. Hattermann • R. Mentlein (*) Department of Anatomy, University of Kiel, Olshausenstraße 40, 24098 Kiel, Germany e-mail: [email protected] A. Sedo and R. Mentlein (eds.), Glioma Cell Biology, DOI 10.1007/978-3-7091-1431-5_6, # Springer-Verlag Wien 2014
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K. Hattermann and R. Mentlein
Keywords
Angiogenesis • Apoptosis • Cancer • Chemotaxis • Imaging • Invasion • Proliferation • Therapy
Abbreviations 7TM receptor ADAM bFGF EGF FCS GDNF GSC HGF/SF IGF IL MAPK MMP PDGF PG PTN RTK Stat TAM TGF TIL VEGF
6.1
Seven transmembrane domain receptor A disintegrin and metalloproteinase Basic fibroblast growth factor Epidermal growth factor Fetal calf serum Glial cell-derived neurotrophic factor Glioma stem(-like) cell Hepatocyte growth factor/scatter factor Insulin-like growth factor Interleukin Mitogen-activated protein kinase Matrix metalloproteinase Platelet-derived growth factor Prostaglandin Pleiotrophin, heparin-binding brain mitogen, heparin-binding growth factor 8 Receptor tyrosine kinase Signal transducer and activator of transcription, s
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