gms | German Medical Science

64th Annual Meeting of the German Society of Neurosurgery (DGNC)

German Society of Neurosurgery (DGNC)

26 - 29 May 2013, Düsseldorf

Cell culture studies of 5-ALA uptake and metabolism in gliomas

Meeting Abstract

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  • Andrei Nemes - Institut für Neuropathologie, Universitätsklinikum Münster, Münster
  • Volker Senner - Institut für Neuropathologie, Universitätsklinikum Münster, Münster
  • Walter Stummer - Klinik für Neurochirurgie, Universitätsklinikum Münster, Münster
  • Christian Ewelt - Klinik für Neurochirurgie, Universitätsklinikum Münster, Münster

Deutsche Gesellschaft für Neurochirurgie. 64. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC). Düsseldorf, 26.-29.05.2013. Düsseldorf: German Medical Science GMS Publishing House; 2013. DocP 139

doi: 10.3205/13dgnc556, urn:nbn:de:0183-13dgnc5564

Published: May 21, 2013

© 2013 Nemes et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Objective: For several years 5-Aminolevulinic acid (5-ALA) induced Protoporhyrin IX (PPIX) fluorescence in malignant brain tumors has been used as an intraoperative marker to improve the grade of total resection. Despite that application, key questions concerning e.g. the heterogenous accumulation of PPIX in the broad group of glioma remain unanswered. Therefore, our research focuses on the differences in intracellular PPIX accumulation in glioma cell lines and between low- and high-grade gliomas. Furthermore, we investigate the cellular 5-ALA uptake machinery and the question: does 5-ALA uptake and metabolism change the behavior of these cells?

Method: Flow cytometry, fluorescence microscopy, RT-PCR and XCelligence proliferation and migration assays.

Results: 5-ALA uptake and metabolism alters the proliferative properties of U373MG and U343MG but not those of U87MG. These findings are in relation to the 5-ALA fluorescence in these cell lines. Fluorescence microscopy and flow cytometry showed distinct variations between U373MG, U343MG and U87MG. Migration, another hallmark of gliomas, was not influenced by 5-ALA in our experimental setting. The di-/tripeptide transporter pept-1 and -2 are reported to be part of the cellular 5-ALA uptake machinery. RT-PCR revealed expression of pept-2 in all three cell lines. So far only pept-2 was shown to be present in GBM cell lines and, in general, in astrocytes. Pept-1 is believed to be only expressed in nephric and intestinal tissues. We found a new form of pept-1 mRNA, that is present in our cell lines. Again, differences in the expression were observed between the strong PPIX fluorescent cell lines U373MG and U343MG in contrast to the weak PPIX fluorescent cell line U87MG. Further experiments with primary cell cultures of low and high-grade gliomas will shed light on the differences, regarding the PPIX fluorescence, between these tumor entities.

Conclusions: To summarize, we investigated different rates of uptake for 5-ALA in glioma cell lines, corresponding with alterations in behavioral properties in glioma. We reported the expression of a new pept-1 RNA variant potentially involved in 5-ALA uptake. Further studies will focus on primary glioma cells, regarding the cellular 5-ALA uptake machinery and behavioral changes especially between low- and high-grade tumors.