TY  - JOUR
A1  - Jennewein, Lukas
A1  - Ronellenfitsch, Michael Wilfried
A1  - Antonietti, Patrick
A1  - Ilina, Elena
A1  - Jung, Jennifer
A1  - Stadel, Daniela
A1  - Flohr, Lisa-Marie
A1  - Zinke, Jenny
A1  - Renesse, Janusz von
A1  - Drott, Ulrich
A1  - Baumgarten, Peter
A1  - Braczynski, Anne Kristin
A1  - Penski, Cornelia
A1  - Burger, Michael Christian
A1  - Theurillat, Jean-Philippe
A1  - Steinbach, Joachim Peter
A1  - Plate, Karl
A1  - Đikić, Ivan
A1  - Fulda, Simone
A1  - Brandts, Christian Hubertus
A1  - Kögel, Donat
A1  - Behrends, Christian
A1  - Harter, Patrick Nikolaus
A1  - Mittelbronn, Michel Guy André
T1  - Diagnostic and clinical relevance of the autophago-lysosomal network in human gliomas
T2  - OncoTarget
N2  - Recently, the conserved intracellular digestion mechanism ‘autophagy’ has been considered to be involved in early tumorigenesis and its blockade proposed as an alternative treatment approach. However, there is an ongoing debate about whether blocking autophagy has positive or negative effects in tumor cells. Since there is only poor data about the clinico-pathological relevance of autophagy in gliomas in vivo, we first established a cell culture based platform for the in vivo detection of the autophago-lysosomal components. We then investigated key autophagosomal (LC3B, p62, BAG3, Beclin1) and lysosomal (CTSB, LAMP2) molecules in 350 gliomas using immunohistochemistry, immunofluorescence, immunoblotting and qPCR. Autophagy was induced pharmacologically or by altering oxygen and nutrient levels. Our results show that autophagy is enhanced in astrocytomas as compared to normal CNS tissue, but largely independent from the WHO grade and patient survival. A strong upregulation of LC3B, p62, LAMP2 and CTSB was detected in perinecrotic areas in glioblastomas suggesting micro-environmental changes as a driver of autophagy induction in gliomas. Furthermore, glucose restriction induced autophagy in a concentration-dependent manner while hypoxia or amino acid starvation had considerably lesser effects. Apoptosis and autophagy were separately induced in glioma cells both in vitro and in vivo. In conclusion, our findings indicate that autophagy in gliomas is rather driven by micro-environmental changes than by primary glioma-intrinsic features thus challenging the concept of exploitation of the autophago-lysosomal network (ALN) as a treatment approach in gliomas.
KW  - LC3B
KW  - apoptosis
KW  - astrocytoma
KW  - autophagy
KW  - glioblastoma
Y1  - 2016
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/40325
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-403254
UR  - http://www.impactjournals.com/oncotarget/misc/linkedout.php?pii=7910
UR  - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4991435
SN  - 1949-2553
N1  - All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
VL  - 7
IS  - 15
SP  - 20016
EP  - 20032
PB  - Impact Journals LLC
CY  - [s. l.]
ER  -