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Diagnostic and clinical relevance of the autophago-lysosomal network in human gliomas.
Journal article

Diagnostic and clinical relevance of the autophago-lysosomal network in human gliomas.

  • Jennewein L Neurological Institute (Edinger Institute), Goethe University, Frankfurt am Main, Germany.
  • Ronellenfitsch MW Senckenberg Institute of Neurooncology, Goethe University, Frankfurt am Main, Germany.
  • Antonietti P Experimental Neurosurgery, Department of Neurosurgery, Goethe University, Frankfurt am Main, Germany.
  • Ilina EI Neurological Institute (Edinger Institute), Goethe University, Frankfurt am Main, Germany.
  • Jung J Institute of Biochemistry II, Goethe University, Frankfurt am Main, Germany.
  • Stadel D Institute of Biochemistry II, Goethe University, Frankfurt am Main, Germany.
  • Flohr LM Neurological Institute (Edinger Institute), Goethe University, Frankfurt am Main, Germany.
  • Zinke J Neurological Institute (Edinger Institute), Goethe University, Frankfurt am Main, Germany.
  • von Renesse J Neurological Institute (Edinger Institute), Goethe University, Frankfurt am Main, Germany.
  • Drott U Neurological Institute (Edinger Institute), Goethe University, Frankfurt am Main, Germany.
  • Baumgarten P Neurological Institute (Edinger Institute), Goethe University, Frankfurt am Main, Germany.
  • Braczynski AK Neurological Institute (Edinger Institute), Goethe University, Frankfurt am Main, Germany.
  • Penski C Neurological Institute (Edinger Institute), Goethe University, Frankfurt am Main, Germany.
  • Burger MC Senckenberg Institute of Neurooncology, Goethe University, Frankfurt am Main, Germany.
  • Theurillat JP Institute of Cell Biology, ETH Zürich, Switzerland.
  • Steinbach JP Senckenberg Institute of Neurooncology, Goethe University, Frankfurt am Main, Germany.
  • Plate KH Neurological Institute (Edinger Institute), Goethe University, Frankfurt am Main, Germany.
  • Dikic I German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Fulda S German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Brandts C German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Kögel D German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Behrends C German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Harter PN Neurological Institute (Edinger Institute), Goethe University, Frankfurt am Main, Germany.
  • Mittelbronn M Neurological Institute (Edinger Institute), Goethe University, Frankfurt am Main, Germany.
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  • 2016-03-10
Published in:
  • Oncotarget. - 2016
LC3B
apoptosis
astrocytoma
autophagy
glioblastoma
Adaptor Proteins, Signal Transducing
Adolescent
Adult
Aged
Aged, 80 and over
Apoptosis Regulatory Proteins
Autophagy
Beclin-1
Biomarkers, Tumor
Brain Neoplasms
Cathepsin B
Child
Child, Preschool
Female
Follow-Up Studies
Glioma
Humans
Infant
Infant, Newborn
Lysosomal-Associated Membrane Protein 2
Lysosomes
Male
Microtubule-Associated Proteins
Middle Aged
Neoplasm Staging
Prognosis
RNA-Binding Proteins
Tumor Cells, Cultured
Young Adult
English 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.
Language
  • English
Open access status
gold
Identifiers
Persistent URL
https://roar.hep-bejune.ch/global/documents/229396
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