New extracellular factors in glioblastoma multiforme development: neurotensin, growth differentiation factor-15, sphingosine-1-phosphate and cytomegalovirus infection

Jan Korbecki, Izabela Gutowska, Ireneusz Kojder, Dariusz Jeżewski, Marta Goschorska, Agnieszka Łukomska, Anna Lubkowska, Dariusz Chlubek and Irena Baranowska-Bosiacka _

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Oncotarget. 2018; 9:7219-7270. https://doi.org/10.18632/oncotarget.24102

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Jan Korbecki1,2, Izabela Gutowska3, Ireneusz Kojder4,5, Dariusz Jeżewski4,5, Marta Goschorska1, Agnieszka Łukomska3, Anna Lubkowska6, Dariusz Chlubek1 and Irena Baranowska-Bosiacka1

1Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland

2Department of Biochemistry and Molecular Biology, Faculty of Health Sciences, University of Bielsko-Biała, 43-309 Bielsko-Biała, Poland

3Department of Biochemistry and Human Nutrition, Pomeranian Medical University in Szczecin, 71-460 Szczecin, Poland

4Department of Applied Neurocognitivistics, Pomeranian Medical University in Szczecin, 71-252 Szczecin, Poland

5Department of Neurosurgery, Pomeranian Medical University in Szczecin, 71-252 Szczecin, Poland

6Department of Functional Diagnostics and Physical Medicine, Pomeranian Medical University in Szczecin, 71-210 Szczecin, Poland

Correspondence to:

Irena Baranowska-Bosiacka, email: [email protected]

Keywords: glioblastoma multiforme; cytomegalovirus; neurotensin; growth differentiation factor-15; sphingosine-1-phosphate

Received: July 12, 2017    Accepted: January 02, 2018    Published: January 09, 2018


Recent years have seen considerable progress in understanding the biochemistry of cancer. For example, more significance is now assigned to the tumor microenvironment, especially with regard to intercellular signaling in the tumor niche which depends on many factors secreted by tumor cells. In addition, great progress has been made in understanding the influence of factors such as neurotensin, growth differentiation factor-15 (GDF-15), sphingosine-1-phosphate (S1P), and infection with cytomegalovirus (CMV) on the ‘hallmarks of cancer’ in glioblastoma multiforme.

Therefore, in the present work we describe the influence of these factors on the proliferation and apoptosis of neoplastic cells, cancer stem cells, angiogenesis, migration and invasion, and cancer immune evasion in a glioblastoma multiforme tumor. In particular, we discuss the effect of neurotensin, GDF-15, S1P (including the drug FTY720), and infection with CMV on tumor-associated macrophages (TAM), microglial cells, neutrophil and regulatory T cells (Treg), on the tumor microenvironment. In order to better understand the role of the aforementioned factors in tumoral processes, we outline the latest models of intratumoral heterogeneity in glioblastoma multiforme. Based on the most recent reports, we discuss the problems of multi-drug therapy in treating glioblastoma multiforme.

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