Artikel
The expression of the neuronal cell adhesion protein L1 (L1CAM) in normal and neoplastic human CNS tissue
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Veröffentlicht: | 2. Juni 2015 |
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Gliederung
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Objective: Diffuse gliomas are highly lethal neoplasms mainly due to their infiltrative growth pattern and resistance to therapy. A cellular subpopulation of gliomas, the glioma stem/tumor-initiating cell is accused of being mainly responsible for treatment resistance. The neuronal cell adhesion molecule L1 (L1CAM, CD171) which regulates proliferation and migration of neural cells as well as axonal outgrowth during normal CNS development was proposed as specific therapeutic target for the glioma-initiating cell fraction. Since most studies were mainly performed in vitro, our aim was to define the in vivo distribution pattern of L1CAM in neoplastic and normal adult and developing brain tissue.
Method: 10 human glioma cell lines were investigated for L1CAM expression by means of immunoblotting and immunocytochemistry. In addition, we investigated 344 astrocytomas including 46 pilocytic astrocytomas (WHO grade I), 13 diffuse astrocytomas (WHO grade II), 33 anaplastic astrocytomas (WHO grade III), 252 glioblastomas (WHO grade IV) and 20 medulloblastomas (WHO grade IV) as well as 3 normal control brains and 18 sections of developing brain tissue.
Results: Most glioma cell lines displayed no (D247, LN308, LN319, U138) or a very weak (LN-18, LN-428, LN-229, U-251, U373) L1CAM expression. Only the A172 showed a strong L1CAM signal. The immunoblotting results perfectly correlated with the immunocytochemical distribution profile on glioma cells. In normal human CNS samples, L1CAM expression was strongly detected within gray matter areas but was markedly decreased at the gray-white matter border. It was then almost absent in the deep white matter, independently from perivascular spaces representing potential stem cell niches. In the developing brain, it was restricted to regions of outgrowing neurites but absent in areas of undifferentiated neuronal precursor cells. In almost all human astrocytomas, a sharp border between L1CAM-negative tumors and infiltrated CNS tissue was observed. In contrast some medulloblastoma specimens (2/10) showed L1CAM positive tumor cells.
Conclusions: In contrast to in vitro studies, L1CAM seems to be largely absent from glioma cells in vivo, especially within the tumor bulks. Interestingly L1CAM is expressed on tumor cells with neuronal differentiation suggesting that its expression goes ahead with neuronal differentiation in normal and neoplastic brain tissue and that L1CAM is not a potential therapeutic target to address glioma initiating cells.